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Hastuti J, Rahmawati NT, Julia M. Childhood High Adiposity has no Advantage for Height in Adulthood: Cross-Sectional Studies in Indonesian Children to Young Adults. Int J Prev Med 2024; 15:64. [PMID: 39742121 PMCID: PMC11687686 DOI: 10.4103/ijpvm.ijpvm_95_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 03/25/2024] [Indexed: 01/03/2025] Open
Abstract
Background Childhood obesity is associated with faster linear growth; nonetheless, its benefit to the mature height of Indonesian children is questionable. This study aimed to evaluate the relationship between adiposity and height growth of Indonesian children, adolescents, and young adults aged 7 to 23 years. Methods Height and skinfolds at triceps, subscapular, suprailiac, and calf were measured in 2,520 children, adolescents, and young adults aged 7 to 23 years (boys = 1,116, girls = 1,404). Central adiposity (subscapular and suprailiac skinfolds) and peripheral adiposity (triceps and calf skinfolds) were projected against heights in each age group. The ANCOVA test and partial correlation were used for statistical analysis. Results With the exception of ages 8 to 12 years, boys were always taller than girls after controlling for age and central or peripheral adiposity. Boys with higher central and peripheral adiposity were taller than their peers up to the age of 17 (r = 0.30-0.72, P < 0.05, P < 0.01). Girls with central adiposity grew taller than their thinner peers until the age of 14 (r = 0.17-0.50, P < 0.05, P < 0.01), whereas girls with peripheral adiposity benefit from this advantage over a more extended period of time. Afterward, adiposity did not offer any benefit on heights. Conclusions Children with high adiposity who were taller at an earlier age have no significant advantage over their thinner peers in terms of adult height.
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Affiliation(s)
- Janatin Hastuti
- Department of Nutrition and Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Neni Trilusiana Rahmawati
- Department of Nutrition and Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Madarina Julia
- Department of Child Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Cho JH, Jung HW, Shim KS. Growth plate closure and therapeutic interventions. Clin Exp Pediatr 2024; 67:553-559. [PMID: 39463341 PMCID: PMC11551597 DOI: 10.3345/cep.2023.00346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 04/19/2024] [Accepted: 05/10/2024] [Indexed: 10/29/2024] Open
Abstract
Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation potential of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon adequate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are depleted, proliferative chondrocyte numbers decrease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and vascularized, the growth plate is closed, and longitudinal bone growth is complete. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further elucidation of these mechanisms will enable the development of new therapeutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.
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Affiliation(s)
- Ja Hyang Cho
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University Hospital, Seoul, Korea
| | - Hae Woon Jung
- Department of Pediatrics, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea
| | - Kye Shik Shim
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University Hospital, Seoul, Korea
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3
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Lee FS, Cruz CJ, Allen KD, Wachs RA. Gait assessment in a female rat Sprague Dawley model of disc-associated low back pain. Connect Tissue Res 2024; 65:407-420. [PMID: 39287332 PMCID: PMC11533987 DOI: 10.1080/03008207.2024.2395287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 08/11/2024] [Accepted: 08/18/2024] [Indexed: 09/19/2024]
Abstract
PURPOSE Gait disturbances are common in human low back pain (LBP) patients, suggesting potential applicability to rodent LBP models. This study aims to assess the influence of disc-associated LBP on gait in female Sprague Dawley rats and explore the utility of the open-source Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) suite as a potential alternative tool for spontaneous pain assessment in a previously established LBP model. MATERIALS AND METHODS Disc degeneration was surgically induced using a one-level disc scrape injury method, and microcomputed tomography was used to assess disc volume loss. After disc injury, axial hypersensitivity was evaluated using the grip strength assay, and an open field test was used to detect spontaneous pain-like behavior. RESULTS Results demonstrated that injured animals exhibit a significant loss in disc volume and reduced grip strength. Open field test did not detect significant differences in distance traveled between sham and injured animals. Concurrently, animals with injured discs did not display significant gait abnormalities in stance time imbalance, temporal symmetry, spatial symmetry, step width, stride length, and duty factor compared to sham. However, comparisons with reference values of normal gait reported in prior literature reveal that injured animals exhibit mild deviations in forelimb and hindlimb stance time imbalance, forelimb temporal symmetry, and hindlimb spatial symmetry at some time points. CONCLUSIONS This study concludes that the disc injury may have very mild effects on gait in female rats within 9 weeks post-injury and recommends future in depth dynamic gait analysis and longer studies beyond 9 weeks to potentially detect gait.
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Affiliation(s)
- Fei San Lee
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, USA
| | - Carlos J Cruz
- J. Crayton Pruitt Family Department of Biomedical Engineering, Biomedical Sciences Building, University of Florida, Gainesville, FL, USA
| | - Kyle D Allen
- J. Crayton Pruitt Family Department of Biomedical Engineering, Biomedical Sciences Building, University of Florida, Gainesville, FL, USA
| | - Rebecca A Wachs
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, USA
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Boğa Kuru B, Akyüz E, Aydın U, Kuru M, Bektaşoğlu F, Sezer M, Yıldız U, Kırmızıbayrak T. Effect of birth type and sex on growth performance, wither height, humerus-radius bone dimensions, humerus-ulna growth plate width and selected hormone profile in growing Gurcu goat kids. Vet Med Sci 2024; 10:e70013. [PMID: 39254122 PMCID: PMC11386322 DOI: 10.1002/vms3.70013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 08/07/2024] [Accepted: 08/23/2024] [Indexed: 09/11/2024] Open
Abstract
OBJECTIVES In this study, the effects of sex and birth type on growth performance, withers height (WH), radiographic measurements and selected hormone profiles in Gurcu goat kids were investigated. METHODS Twenty kids (single female = 5, single male = 5, twin female = 5, twin male = 5) were included in the study. Body weight (BW), WH, radiographic measurements (humerus length [HL], radius length [RL], proximal humerus epiphyseal plate width [HEP] and distal ulna epiphyseal plate width [UEP]) and biochemical analysis (for serum calcitonin, free triiodothyronine [FT3], free thyroxine [FT4], growth hormone [GH] and insulin-like growth factor-I [IGF-I]) were performed at 1, 3, 5, 7, 9 and 12 months of age. RESULTS BW was significantly higher in males starting from the seventh month compared to females (p < 0.05). HL was higher in males at seventh (p = 0.009) and ninth (p = 0.033) months, whereas RL was lower in twins at the third month (p = 0.021). UEP was wider in males at seventh (p = 0.008) and ninth (p = 0.036) months. Closure of HEP was observed in 65% of kids by the 12th month. Calcitonin was lower in twins at third (p = 0.045) and fifth (p = 0.006) months, with changes observed due to group and time effects (p < 0.05), whereas other hormones only changed with time (p < 0.05). Positive correlations were observed between BW, WH, HL, RL and IGF-I. There was a negative correlation between BW, WH, HL, RL, IGF-I and HEP, UEP, calcitonin, FT3, FT4, GH. CONCLUSION Sex and birth type in Gurcu goat kids may have an impact on growth performance, radiographic measurements and certain hormonal profiles.
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Affiliation(s)
- Buket Boğa Kuru
- Department of Animal Breeding and HusbandryFaculty of Veterinary Medicine, Kafkas UniversityKarsTurkey
| | - Enes Akyüz
- Department of Internal MedicineFaculty of Veterinary Medicine, Kafkas UniversityKarsTurkey
| | - Uğur Aydın
- Department of SurgeryFaculty of Medicine, Kafkas UniversityKarsTurkey
| | - Mushap Kuru
- Department of Obstetrics and GynecologyFaculty of Veterinary Medicine, Kafkas UniversityKarsTurkey
| | - Fikret Bektaşoğlu
- Department of Animal Breeding and HusbandryFaculty of Veterinary Medicine, Kafkas UniversityKarsTurkey
| | - Mert Sezer
- Department of Internal MedicineFaculty of Veterinary Medicine, Kafkas UniversityKarsTurkey
| | - Uğur Yıldız
- Department of SurgeryFaculty of Medicine, Kafkas UniversityKarsTurkey
| | - Turgut Kırmızıbayrak
- Department of Animal Breeding and HusbandryFaculty of Veterinary Medicine, Kafkas UniversityKarsTurkey
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Sun Q, Huang J, Tian J, Lv C, Li Y, Yu S, Liu J, Zhang J. Key Roles of Gli1 and Ihh Signaling in Craniofacial Development. Stem Cells Dev 2024; 33:251-261. [PMID: 38623785 DOI: 10.1089/scd.2024.0036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024] Open
Abstract
The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation and decreased ossification and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. In addition, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues. This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.
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Affiliation(s)
- Qi Sun
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
- Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Jie Huang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
- Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Jingjun Tian
- Department of Orthodontics, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Changhai Lv
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Yanhong Li
- Department of Preventive Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Siyuan Yu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Juan Liu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
- Department of Preventive Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
| | - Jun Zhang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
- Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, Yunnan, Republic of China
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Lu D, Zeng L, Li Y, Gu R, Hu M, Zhang P, Yu P, Zhang X, Xie Z, Liu H, Zhou Y. Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways. Animal Model Exp Med 2024; 7:208-221. [PMID: 38013618 PMCID: PMC11228090 DOI: 10.1002/ame2.12359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/16/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength. However, current anti-resorptive drugs carry a risk of various complications. The deep learning-based efficacy prediction system (DLEPS) is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes. This study aimed to explore the protective effect and potential mechanisms of cinobufotalin (CB), a traditional Chinese medicine (TCM), on bone loss. METHODS DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis. Micro-CT, histological and morphological analysis were applied for the bone protective detection of CB, and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells (hBMMSCs) were also investigated. The underlying mechanism was verified using qRT-PCR, Western blot (WB), immunofluorescence (IF), etc. RESULTS: A safe concentration (0.25 mg/kg in vivo, 0.05 μM in vitro) of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs. Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation, further regulating the expression of osteogenesis-associated factors, and ultimately promoting osteogenesis. CONCLUSION Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss, further promoting osteogenic differentiation/function of hBMMSCs, with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
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Affiliation(s)
- Da‐zhuang Lu
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Li‐jun Zeng
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Yang Li
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Ran‐li Gu
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Meng‐long Hu
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Ping Zhang
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Peng Yu
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
- Department of Cariology and EndodontologyPeking University School and Hospital of StomatologyBeijingChina
| | - Xiao Zhang
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
| | - Zheng‐wei Xie
- Peking University International Cancer InstitutePeking University Health Science Center, Peking UniversityBeijingChina
| | - Hao Liu
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
- Central LaboratoryPeking University School and Hospital of StomatologyBeijingChina
| | - Yong‐sheng Zhou
- Department of ProsthodonticsPeking University School and Hospital of StomatologyBeijingChina
- National Center of StomatologyBeijingChina
- National Clinical Research Center for Oral DiseasesBeijingChina
- Beijing Key Laboratory of Digital StomatologyBeijingChina
- Central LaboratoryPeking University School and Hospital of StomatologyBeijingChina
- National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina
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Asmussen NC, Cohen DJ, Boyan BD, Schwartz Z. Regulatory Pathways in Growth Plate Chondrocytes that Are Impacted by Matrix Vesicle microRNA Identified by Targeted RISC Pulldown and Sequencing of the Resulting Transcriptome. Calcif Tissue Int 2024; 114:409-418. [PMID: 38315223 PMCID: PMC10957581 DOI: 10.1007/s00223-023-01179-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/23/2023] [Indexed: 02/07/2024]
Abstract
During endochondral bone formation, growth plate chondrocytes are differentially regulated by various factors and hormones. As the cellular phenotype changes, the composition of the extracellular matrix is altered, including the production and composition of matrix vesicles (MV) and their cargo of microRNA. The regulatory functions of these MV microRNA in the growth plate are still largely unknown. To address this question, we undertook a targeted bioinformatics approach. A subset of five MV microRNA was selected for analysis based on their specific enrichment in these extracellular vesicles compared to the parent cells (miR-1-3p, miR-22-3p, miR-30c-5p, miR-122-5p, and miR-133a-3p). Synthetic biotinylated versions of the microRNA were produced using locked nucleic acid (LNA) and were transfected into rat growth plate chondrocytes. The resulting LNA to mRNA complexes were pulled down and sequenced, and the transcriptomic data were used to run pathway analysis pipelines. Bone and musculoskeletal pathways were discovered to be regulated by the specific microRNA, notably those associated with transforming growth factor beta (TGFβ) and Wnt pathways, cell differentiation and proliferation, and regulation of vesicles and calcium transport. These results can help with understanding the maturation of the growth plate and the regulatory role of microRNA in MV.
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Affiliation(s)
- Niels C Asmussen
- School of Integrative Life Sciences, Virginia Commonwealth University, Richmond, VA, USA
| | - David J Cohen
- College of Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA, 23284, USA
| | - Barbara D Boyan
- College of Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA, 23284, USA.
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
| | - Zvi Schwartz
- College of Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA, 23284, USA
- Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Abstract
PURPOSE OF REVIEW Here, we discuss the origin of chondrocytes, their destiny, and their plasticity in relationship to bone growth, articulation, and formation of the trabeculae. We also consider these processes from a biological, clinical, and evolutionary perspective. RECENT FINDINGS Chondrocytes, which provide the template for the formation of most bones, are responsible for skeletal growth and articulation during postnatal life. In recent years our understanding of the fate of these cells has changed dramatically. Current evidence indicates a paradoxical situation during skeletogenesis, with some cells of mesenchymal condensation differentiating directly into osteoblasts, whereas others of the same kind give rise to highly similar osteoblasts via a complex process of differentiation involving several chondrocyte intermediates. The situation becomes even more paradoxical during postnatal growth when stem cells in the growth plate produce differentiated, functional progenies, which thereafter presumably dedifferentiate into another type of stem cell. Such a remarkable transition from one cell type to another under postnatal physiological conditions provides a fascinating example of cellular plasticity that may have valuable clinical implications.
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Affiliation(s)
- Andrei S Chagin
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
| | - Tsz Long Chu
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
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Fedorczak A, Lewiński A, Stawerska R. Involvement of Sirtuin 1 in the Growth Hormone/Insulin-like Growth Factor 1 Signal Transduction and Its Impact on Growth Processes in Children. Int J Mol Sci 2023; 24:15406. [PMID: 37895086 PMCID: PMC10607608 DOI: 10.3390/ijms242015406] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/01/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023] Open
Abstract
The regulation of growth processes in children depends on the synthesis of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Insulin-like growth factor 1, which is mainly secreted in the liver in response to GH, is the main peripheral mediator of GH action. Newly discovered factors regulating GH secretion and its effects are being studied recently. One of them is sirtuin 1 (SIRT1). This NAD+-dependent deacetylase, by modulating the JAK2/STAT pathway, is involved in the transduction of the GH signal in hepatocytes, leading to the synthesis of IGF-1. In addition, it participates in the regulation of the synthesis of GHRH in the hypothalamus and GH in the somatotropic cells. SIRT1 is suggested to be involved in growth plate chondrogenesis and longitudinal bone growth as it has a positive effect on the epiphyseal growth plate. SIRT1 is also implicated in various cellular processes, including metabolism, cell cycle regulation, apoptosis, oxidative stress response, and DNA repair. Thus, its expression varies depending on the different metabolic states. During malnutrition, SIRT1 blocks GH signal transduction in hepatocytes to reduce the IGF-1 secretion and prevent hypoglycemia (i.e., it causes transient GH resistance). In this review, we focused on the influence of SIRT1 on GH signal transduction and the implications that may arise for growth processes in children.
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Affiliation(s)
- Anna Fedorczak
- Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland
| | - Andrzej Lewiński
- Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland
- Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 93-338 Lodz, Poland
| | - Renata Stawerska
- Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland
- Department of Paediatric Endocrinology, Medical University of Lodz, 93-338 Lodz, Poland
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10
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Asmussen NC, Alam S, Lin Z, Cohen DJ, Schwartz Z, Boyan BD. 1α,25-Dihydroxyvitamin D 3 Regulates microRNA Packaging in Extracellular Matrix Vesicles and Their Release in the Matrix. Calcif Tissue Int 2023; 112:493-511. [PMID: 36840756 DOI: 10.1007/s00223-023-01067-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 01/30/2023] [Indexed: 02/26/2023]
Abstract
Growth plate chondrocytes are regulated by numerous factors and hormones as they mature during endochondral bone formation, including transforming growth factor beta-1 (TGFb1), bone morphogenetic protein 2 (BMP2), insulin-like growth factor-1 (IFG1), parathyroid hormone and parathyroid hormone related peptide (PTH, PTHrP), and Indian hedgehog (IHH). Chondrocytes in the growth plate's growth zone (GC) produce and export matrix vesicles (MVs) under the regulation of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. 1α,25(OH)2D3 regulates MV enzyme composition genomically and 1α,25(OH)2D3 secreted by the cells acts on the MV membrane nongenomically, destabilizing it and releasing MV enzymes. This study examined the regulatory role 1α,25(OH)2D3 has over production and packaging of microRNA (miRNA) into MVs by GC cells and the release of miRNA by direct action on MVs. Costochondral cartilage GC cells were treated with 1α,25(OH)2D3 and the miRNA in the cells and MVs sequenced. We also treated MVs with 1α,25(OH)2D3 and determined if the miRNA was released. To assess whether MVs can act directly with chondrocytes and if this is regulated by 1α,25(OH)2D3, we stained MVs with a membrane dye and treated GC cells with them. 1α,25(OH)2D3 regulated production and packaging of a unique population of miRNA into MVs compared to the vehicle control population. 1α,25(OH)2D3 treatment of MVs did not release miRNA. Stained MVs were endocytosed by GC cells and this was increased with 1α,25(OH)2D3 treatment. This study adds new regulatory roles for 1α,25(OH)2D3 with respect to packaging and transport of MV miRNAs.
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Affiliation(s)
- Niels C Asmussen
- School of Integrative Life Sciences, Virginia Commonwealth University, Richmond, VA, USA
| | - Sheikh Alam
- School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA
| | - Zhao Lin
- School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA
| | - David J Cohen
- College of Engineering, Virginia Commonwealth University, Richmond, VA, USA
| | - Zvi Schwartz
- College of Engineering, Virginia Commonwealth University, Richmond, VA, USA
- Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Barbara D Boyan
- College of Engineering, Virginia Commonwealth University, Richmond, VA, USA.
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
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Nelson JM, Compton SD, Farahzad MM, Winfrey OK, Rosen MW. The relationship between estrogen and subsequent growth restriction among adolescents with heavy menstrual bleeding at menarche. J Pediatr Endocrinol Metab 2023; 36:255-260. [PMID: 36727420 DOI: 10.1515/jpem-2022-0536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 01/15/2023] [Indexed: 02/03/2023]
Abstract
OBJECTIVES We sought to evaluate the impact of estrogen-containing treatment for heavy menstrual bleeding (HMB) on subsequent height compared to progesterone-only or non-hormonal treatment when initiated at menarche. METHODS We performed a retrospective chart review of adolescent females aged 10-15 years who presented to an institution-affiliated outpatient, inpatient, or emergency setting for management of HMB within three months of menarche. Growth records over a 2 year period starting at menarche were recorded, and comparisons made among patients treated with 1) estrogen, 2) progesterone, and 3) non-hormonal methods (controls). Groups were compared using bivariate analysis with Chi-square or Fisher's exact test and linear regression. RESULTS In an analysis of 80 patients at 24 months, the mean increase in height from menarche was 6.4 cm among controls (n=54), 7.2 cm among the progesterone-only group (n=10), and 3.8 cm among the estrogen group (n=16). The estrogen group's increase in height was significantly lower than the control group's, by a mean of 1.8 cm (p=0.04). Change in height did not differ significantly between the progesterone and control groups (p=0.87). Additionally, for every year younger at menarche, there was 1 fewer cm of growth (change in height) at 24 months after menarche (p<0.002). CONCLUSIONS Estrogen-containing treatment for HMB initiated within three months of menarche was associated with reduced growth at 24 months compared to progesterone-only or non-hormonal methods. The clinical applicability of the estrogen group's 1.8 cm absolute reduction in height may have considerable significance for those who are shorter at baseline.
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Affiliation(s)
- Jessie M Nelson
- Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Sarah D Compton
- Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Mina M Farahzad
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
| | - Olivia K Winfrey
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
| | - Monica W Rosen
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
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12
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Trujillo MV, Lee PA, Reifschneider K, Backeljauw PF, Dragnic S, Van Komen S, Yu J, Klein KO. Using change in predicted adult height during GnRH agonist treatment for individualized treatment decisions in girls with central precocious puberty. J Pediatr Endocrinol Metab 2023; 36:299-308. [PMID: 36473097 DOI: 10.1515/jpem-2022-0476] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 11/10/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVES It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care. METHODS Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models. RESULTS BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months). CONCLUSIONS These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH.
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Affiliation(s)
- Marcela Vargas Trujillo
- Department of Pediatrics, University of California San Diego, and Rady Children's Hospital, San Diego, CA, USA
| | - Peter A Lee
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Penn State Hershey Medical Center, Hershey, PA, USA
| | | | - Philippe F Backeljauw
- Division of Endocrinology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | | | | | - Jun Yu
- AbbVie, North Chicago, IL, USA
| | - Karen O Klein
- Department of Pediatrics, University of California San Diego, and Rady Children's Hospital, San Diego, CA, USA
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13
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Brent MB. Pharmaceutical treatment of bone loss: From animal models and drug development to future treatment strategies. Pharmacol Ther 2023; 244:108383. [PMID: 36933702 DOI: 10.1016/j.pharmthera.2023.108383] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 02/18/2023] [Accepted: 03/09/2023] [Indexed: 03/17/2023]
Abstract
Animal models are fundamental to advance our knowledge of the underlying pathophysiology of bone loss and to study pharmaceutical countermeasures against it. The animal model of post-menopausal osteoporosis from ovariectomy is the most widely used preclinical approach to study skeletal deterioration. However, several other animal models exist, each with unique characteristics such as bone loss from disuse, lactation, glucocorticoid excess, or exposure to hypobaric hypoxia. The present review aimed to provide a comprehensive overview of these animal models to emphasize the importance and significance of investigating bone loss and pharmaceutical countermeasures from perspectives other than post-menopausal osteoporosis only. Hence, the pathophysiology and underlying cellular mechanisms involved in the various types of bone loss are different, and this might influence which prevention and treatment strategies are the most effective. In addition, the review sought to map the current landscape of pharmaceutical countermeasures against osteoporosis with an emphasis on how drug development has changed from being driven by clinical observations and enhancement or repurposing of existing drugs to today's use of targeted anti-bodies that are the result of advanced insights into the underlying molecular mechanisms of bone formation and resorption. Moreover, new treatment combinations or repurposing opportunities of already approved drugs with a focus on dabigatran, parathyroid hormone and abaloparatide, growth hormone, inhibitors of the activin signaling pathway, acetazolamide, zoledronate, and romosozumab are discussed. Despite the considerable progress in drug development, there is still a clear need to improve treatment strategies and develop new pharmaceuticals against various types of osteoporosis. The review also highlights that new treatment indications should be explored using multiple animal models of bone loss in order to ensure a broad representation of different types of skeletal deterioration instead of mainly focusing on primary osteoporosis from post-menopausal estrogen deficiency.
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Affiliation(s)
- Mikkel Bo Brent
- Department of Biomedicine, Aarhus University, Denmark, Wilhelm Meyers Allé 3, 8000 Aarhus C, Denmark.
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14
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Longitudinal effects of estrogen on mandibular growth and changes in cartilage during the growth period in rats. Dev Biol 2022; 492:126-132. [DOI: 10.1016/j.ydbio.2022.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 09/08/2022] [Accepted: 10/10/2022] [Indexed: 11/19/2022]
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15
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Wang J, Kokinos BP, Lang PJ, Crenshaw TD, Henak CR. Vitamin D deficiency and anatomical region alters porcine growth plate properties. J Biomech 2022; 144:111314. [PMID: 36182792 DOI: 10.1016/j.jbiomech.2022.111314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/12/2022] [Accepted: 09/16/2022] [Indexed: 11/19/2022]
Abstract
Ossification of growth plate cartilage mediates longitudinal extension of long bones. Biomechanical and biochemical disruptions of growth plate function may lead to abnormal bone growth. In humans and animals, severe dietary vitamin D deficiency can lead to rickets which features growth plate widening, resulting in abnormalities in growth. However, effects of marginal vitamin D deficiencies on growth plates are not well understood. The purpose of this study was to examine the effects of a vitamin D deficient diet in the 26-day nursery phase on mechanical properties (ultimate normal stress, ultimate shear stress, ultimate strain, and tangent modulus) of porcine growth plate. Standard uniaxial tensile tests were applied on bone-growth plate-bone sections and the total stress was decomposed into normal stress and shear stress. Ultimate shear stress and ultimate strain traits were lower in the vitamin D deficient group than in the control. Regional differences were observed in all four variables. Ultimate normal stress was higher in the anterior region, which was consistent with a previous study. Sex differences were detected in ultimate normal stress, which was higher in females than in males. Interestingly, the classical finding of growth plate widening seen in severe vitamin D deficiency was not observed in the pigs with marginal vitamin D deficiency utilized in this study.
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Affiliation(s)
- Jingyi Wang
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI, United States
| | - Brittney P Kokinos
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States
| | - Pamela J Lang
- Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States
| | - Thomas D Crenshaw
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States
| | - Corinne R Henak
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI, United States; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States.
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16
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Yan X, Fan D, Pi Y, Zhang Y, Fu P, Zhang H. ERα/β/DMP1 axis promotes trans-differentiation of chondrocytes to bone cells through GSK-3β/β-catenin pathway. J Anat 2022; 240:1152-1161. [PMID: 35081258 PMCID: PMC9119614 DOI: 10.1111/joa.13612] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/04/2021] [Accepted: 12/06/2021] [Indexed: 02/06/2023] Open
Abstract
Estrogen-induced premature closing of the growth plate in the long bones is a major cause of short stature after premature puberty. Recent studies have found that chondrocytes can directly trans-differentiate into osteoblasts in the process of endochondral bone formation, which indicates that cartilage formation and osteogenesis may be a continuous biological process. However, whether estrogen promotes the direct trans-differentiation of chondrocytes into osteoblasts remains largely unknown. Chondrocytes were treated with different concentrations of 17β-estradiol, and Alizarin Red staining and alkaline phosphatase activity assay were used to detected osteogenesis. Specific short hairpin RNA and tamoxifen were used to block the estrogen receptor (ER) pathway and osteogenic marker genes and downstream gene expression were detected using real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining. The findings showed that 17β-estradiol promoted the chondrocyte osteogenesis in vitro, even at high concentrations. In addition, blocking of the ERα/β pathway inhibited the trans-differentiation of chondrocytes into osteogenic cells. Furthermore, we found that dentin matrix protein 1 (DMP1), which is a direct downstream molecular of ER, was involved in 17β-estradiol/ER pathway-regulated osteogenesis. As well, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signal pathway also participates in ERα/β/DMP1-regulated chondrocyte osteogenesis. The GSK-3β/β-catenin signal pathway was involved in ERα/β/DMP1-regulated chondrocyte osteogenesis. These findings suggest that ER/DMP1/GSK-3β/β-catenin plays a vital role in estrogen regulation of chondrocyte osteogenesis and provide a therapeutic target for short stature caused by epiphyseal fusion.
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Affiliation(s)
- Xue Yan
- Department of PediatricsThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Deng‐Yun Fan
- Department of PediatricsThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Ya‐Lei Pi
- Department of PediatricsThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Ya‐Nan Zhang
- Department of PediatricsThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Peng‐Jiu Fu
- Department of PediatricsThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Hui‐Feng Zhang
- Department of PediatricsThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
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17
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Boyan BD, Asmussen NC, Lin Z, Schwartz Z. The Role of Matrix-Bound Extracellular Vesicles in the Regulation of Endochondral Bone Formation. Cells 2022; 11:1619. [PMID: 35626656 PMCID: PMC9139584 DOI: 10.3390/cells11101619] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/01/2022] [Accepted: 05/09/2022] [Indexed: 02/04/2023] Open
Abstract
Matrix vesicles are key players in the development of the growth plate during endochondral bone formation. They are involved in the turnover of the extracellular matrix and its mineralization, as well as being a vehicle for chondrocyte communication and regulation. These extracellular organelles are released by the cells and are anchored to the matrix via integrin binding to collagen. The exact function and makeup of the vesicles are dependent on the zone of the growth plate in which they are produced. Early studies defined their role as sites of initial calcium phosphate deposition based on the presence of crystals on the inner leaflet of the membrane and subsequent identification of enzymes, ion transporters, and phospholipid complexes involved in mineral formation. More recent studies have shown that they contain small RNAs, including microRNAs, that are distinct from the parent cell, raising the hypothesis that they are a distinct subset of exosomes. Matrix vesicles are produced under complex regulatory pathways, which include the action of steroid hormones. Once in the matrix, their maturation is mediated by the action of secreted hormones. How they convey information to cells, either through autocrine or paracrine actions, is now being elucidated.
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Affiliation(s)
- Barbara D. Boyan
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA;
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Niels C. Asmussen
- School of Integrated Life Sciences, Virginia Commonwealth University, Richmond, VA 23284, USA;
| | - Zhao Lin
- Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23284, USA;
| | - Zvi Schwartz
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA;
- Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
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18
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Mandal D, Ray U, Ghosh P. Differences in skeletal growth pattern of yoga practising adolescent girls: A cross-sectional study. J Ayurveda Integr Med 2022; 13:100550. [PMID: 35255268 PMCID: PMC8904604 DOI: 10.1016/j.jaim.2022.100550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 04/26/2021] [Accepted: 01/23/2022] [Indexed: 11/28/2022] Open
Abstract
Background Yogasana improves both mental and physical health. There is sparse systematic research on the growth of yogasana practising adolescents. Objectives This study aims to assess the differential skeletal growth pattern among pre-adolescent and adolescent girls as a result of yoga practice. Methods A cross-sectional anthropometric study was conducted on stature (height), sitting height and leg length of 757 school-going girls (4-15 years old), divided in two groups, Yoga Group (YG) (n=380) and age matched Control Group (CG) (n=377) participants participating in recreational games other than yoga. Descriptive and inferential statistical analyses were applied. Unpaired t-test was performed for assessment of level of significance and Pearson's correlation (r) test was performed to to identify the association between growth pattern of stature and leg length at specific ages. Results The physical growth showed an ascending trend in both Yoga group (YG)2 participants and control group (CG)3 . At the onset of adolescence (10–12 years) the mean stature and leg length of YG participants were retarded (p < 0.05). Sitting height in YG was significantly (p < 0.05) low only in 10-year-olds. The similar trends were observed in stature and leg length in YG participants at 10 years (5th and 10th percentile) and 12 years (90th and 95th percentile). There was strong positive relationship between stature and leg length of YG participants (10 years, r = 0.86, p < 0.01; 11 years, r = 0.86, p < 0.01; 12 years, r = 0.72, p < 0.01). The stunted growth in YG participants during adolescence may be related to retarded growth of leg length. Conclusions Intense yogasana practice with greater skeletal stress possibly hinders stature in adolescent girls from 10 to 12 years. This may compromise with the natural growth pattern, necessitating special care during yoga training among adolescents while selecting the type, intensity and duration of yogasanas practice.
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Affiliation(s)
- Debjani Mandal
- Department of Physiology, West Bengal State University, Barasat, Kolkata, 700126, India
| | - UdaySankar Ray
- Department of Physiology, West Bengal State University, Barasat, Kolkata, 700126, India
| | - Pratiti Ghosh
- Department of Physiology, West Bengal State University, Barasat, Kolkata, 700126, India.
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19
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Kazemi M, Williams JL. Properties of Cartilage-Subchondral Bone Junctions: A Narrative Review with Specific Focus on the Growth Plate. Cartilage 2021; 13:16S-33S. [PMID: 32458695 PMCID: PMC8804776 DOI: 10.1177/1947603520924776] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE The purpose of this narrative review is to summarize what is currently known about the structural, chemical, and mechanical properties of cartilage-bone interfaces, which provide tissue integrity across a bimaterial interface of 2 very different structural materials. Maintaining these mechanical interfaces is a key factor for normal bone growth and articular cartilage function and maintenance. MATERIALS AND METHODS A comprehensive search was conducted using Google Scholar and PubMed/Medline with a specific focus on the growth plate cartilage-subchondral bone interface. All original articles, reviews in journals, and book chapters were considered. Following a review of the overall structural and functional characteristics of the physis, the literature on histological studies of both articular and growth plate chondro-osseous junctions is briefly reviewed. Next the literature on biochemical properties of these interfaces is reviewed, specifically the literature on elemental analyses across the cartilage-subchondral bone junctions. The literature on biomechanical studies of these junctions at the articular and physeal interfaces is also reviewed and compared. RESULTS Unlike the interface between articular cartilage and bone, growth plate cartilage has 2 chondro-osseous junctions. The reserve zone of the mature growth plate is intimately connected to a plate of subchondral bone on the epiphyseal side. This interface resembles that between the subchondral bone and articular cartilage, although much less is known about its makeup and formation. CONCLUSION There is a notably paucity of information available on the structural and mechanical properties of reserve zone-subchondral epiphyseal bone interface. This review reveals that further studies are needed on the microstructural and mechanical properties of chondro-osseous junction with the reserve zone.
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Affiliation(s)
- Masumeh Kazemi
- Biomedical Engineering Department,
University of Memphis, Memphis, TN, USA,Masumeh Kazemi, Biomedical Engineering
Department, University of Memphis, 3796 Norriswood Avenue, Memphis, TN 38152,
USA.
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20
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Farid M, Shibu M. A rare case of Seymour fracture in an adult with non-fused growth plates. CASE REPORTS IN PLASTIC SURGERY AND HAND SURGERY 2021; 8:72-75. [PMID: 34104672 PMCID: PMC8143599 DOI: 10.1080/23320885.2021.1927738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The mechanism for growth plate fusion is not fully understood yet. We present the first reported Seymour fracture (Salter Harris I) in an adult with failed growth plate fusion. The management of Seymour fractures should be according to radiological bone age rather than actual age.
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Affiliation(s)
- Mohammed Farid
- Plastic Surgery, Queen Elizabeth Hospital, Birmingham, UK
| | - Mohamed Shibu
- Plastic Surgery, The Royal London Hospital, London, UK
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21
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Park J, Choi JY, Choi J, Chung S, Song N, Park SK, Han W, Noh DY, Ahn SH, Lee JW, Kim MK, Jee SH, Wen W, Bolla MK, Wang Q, Dennis J, Michailidou K, Shah M, Conroy DM, Harrington PA, Mayes R, Czene K, Hall P, Teras LR, Patel AV, Couch FJ, Olson JE, Sawyer EJ, Roylance R, Bojesen SE, Flyger H, Lambrechts D, Baten A, Matsuo K, Ito H, Guénel P, Truong T, Keeman R, Schmidt MK, Wu AH, Tseng CC, Cox A, Cross SS, kConFab Investigators, Andrulis IL, Hopper JL, Southey MC, Wu PE, Shen CY, Fasching PA, Ekici AB, Muir K, Lophatananon A, Brenner H, Arndt V, Jones ME, Swerdlow AJ, Hoppe R, Ko YD, Hartman M, Li J, Mannermaa A, Hartikainen JM, Benitez J, González-Neira A, Haiman CA, Dörk T, Bogdanova NV, Teo SH, Mohd Taib NA, Fletcher O, Johnson N, Grip M, Winqvist R, Blomqvist C, Nevanlinna H, Lindblom A, Wendt C, Kristensen VN, NBCS Collaborators, Tollenaar RAEM, Heemskerk-Gerritsen BAM, Radice P, Bonanni B, Hamann U, Manoochehri M, Lacey JV, Martinez ME, Dunning AM, Pharoah PDP, Easton DF, Yoo KY, Kang D. Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies? Cancers (Basel) 2021; 13:2370. [PMID: 34069208 PMCID: PMC8156547 DOI: 10.3390/cancers13102370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 04/29/2021] [Accepted: 04/30/2021] [Indexed: 12/24/2022] Open
Abstract
In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10-3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10-4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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Affiliation(s)
- JooYong Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; (J.P.); (S.C.); (S.K.P.); (D.K.)
- BK21plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Ji-Yeob Choi
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; (J.P.); (S.C.); (S.K.P.); (D.K.)
- BK21plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, Korea
- Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul 03080, Korea;
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (W.H.); (D.-Y.N.)
| | - Jaesung Choi
- Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul 03080, Korea;
| | - Seokang Chung
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; (J.P.); (S.C.); (S.K.P.); (D.K.)
| | - Nan Song
- College of Pharmacy, Chungbuk National University, Cheongju-si 28160, Korea;
| | - Sue K. Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; (J.P.); (S.C.); (S.K.P.); (D.K.)
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (W.H.); (D.-Y.N.)
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Wonshik Han
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (W.H.); (D.-Y.N.)
- Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Dong-Young Noh
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (W.H.); (D.-Y.N.)
- Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Sei-Hyun Ahn
- Department of Surgery, Medicine and ASAN Medical Center, University of Ulsan College, Seoul 05505, Korea; (S.-H.A.); (J.W.L.)
| | - Jong Won Lee
- Department of Surgery, Medicine and ASAN Medical Center, University of Ulsan College, Seoul 05505, Korea; (S.-H.A.); (J.W.L.)
| | - Mi Kyung Kim
- Division of Cancer Epidemiology and Management, National Cancer Center, Goyang-si 10408, Korea;
| | - Sun Ha Jee
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 03722, Korea;
| | - Wanqing Wen
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
| | - Manjeet K. Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK; (M.K.B.); (Q.W.); (J.D.); (K.M.); (P.D.P.P.); (D.F.E.)
| | - Qin Wang
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK; (M.K.B.); (Q.W.); (J.D.); (K.M.); (P.D.P.P.); (D.F.E.)
| | - Joe Dennis
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK; (M.K.B.); (Q.W.); (J.D.); (K.M.); (P.D.P.P.); (D.F.E.)
| | - Kyriaki Michailidou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK; (M.K.B.); (Q.W.); (J.D.); (K.M.); (P.D.P.P.); (D.F.E.)
- Biostatistics Unit, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus
- Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, Nicosia 23462, Cyprus
| | - Mitul Shah
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Don M. Conroy
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Patricia A. Harrington
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Rebecca Mayes
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65 Stockholm, Sweden; (K.C.); (P.H.)
| | - Per Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65 Stockholm, Sweden; (K.C.); (P.H.)
- Department of Oncology, Södersjukhuset, 118 83 Stockholm, Sweden
| | - Lauren R. Teras
- Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA;
| | - Alpa V. Patel
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; (A.V.P.); (F.J.C.)
| | - Fergus J. Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; (A.V.P.); (F.J.C.)
| | - Janet E. Olson
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;
| | - Elinor J. Sawyer
- School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy’s Campus, King’s College London, London SE1 9RT, UK;
| | - Rebecca Roylance
- Department of Oncology, UCLH Foundation Trust, London NW1 2PG, UK;
| | - Stig E. Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark;
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Henrik Flyger
- Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark;
| | - Diether Lambrechts
- VIB Center for Cancer Biology, 3001 Leuve, Belgium;
- Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium
| | - Adinda Baten
- Department of Radiotherapy Oncology, KU Leuven—University of Leuven, University Hospitals Leuven, 3000 Leuven, Belgium;
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan;
- Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;
| | - Hidemi Ito
- Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;
| | - Pascal Guénel
- Center for Research in Epidemiology and Population Health (CESP), Team Exposome and Heredity, INSERM, University Paris-Saclay, 94805 Villejuif, France; (P.G.); (T.T.)
| | - Thérèse Truong
- Center for Research in Epidemiology and Population Health (CESP), Team Exposome and Heredity, INSERM, University Paris-Saclay, 94805 Villejuif, France; (P.G.); (T.T.)
| | - Renske Keeman
- Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands; (R.K.); (M.K.S.)
| | - Marjanka K. Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands; (R.K.); (M.K.S.)
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
| | - Anna H. Wu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; (A.H.W.); (C.-C.T.); (C.A.H.)
| | - Chiu-Chen Tseng
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; (A.H.W.); (C.-C.T.); (C.A.H.)
| | - Angela Cox
- Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2TN, UK;
| | - Simon S. Cross
- Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK;
| | - kConFab Investigators
- Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia;
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3000, Australia
| | - Irene L. Andrulis
- Fred A, Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada;
- Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
| | - John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia;
| | - Melissa C. Southey
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia;
- Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC 3010, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia
| | - Pei-Ei Wu
- Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan;
| | - Chen-Yang Shen
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan;
- School of Public Health, China Medical University, Taichung 404, Taiwan
| | - Peter A. Fasching
- Department of Medicine Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany
| | - Arif B. Ekici
- Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany;
| | - Kenneth Muir
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK; (K.M.); (A.L.)
| | - Artitaya Lophatananon
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK; (K.M.); (A.L.)
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (H.B.); (V.A.)
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (H.B.); (V.A.)
| | - Michael E. Jones
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK; (M.E.J.); (A.J.S.)
| | - Anthony J. Swerdlow
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK; (M.E.J.); (A.J.S.)
- Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK
| | - Reiner Hoppe
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany;
- University of Tübingen, 72074 Tübingen, Germany
| | - Yon-Dschun Ko
- Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53177 Bonn, Germany;
| | - Mikael Hartman
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore;
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore
- Department of Surgery, National University Health System, Singapore 119228, Singapore
| | - Jingmei Li
- Human Genetics Division, Genome Institute of Singapore, Singapore 138672, Singapore;
| | - Arto Mannermaa
- Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland; (A.M.); (J.M.H.)
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland
- Biobank of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, Finland
| | - Jaana M. Hartikainen
- Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland; (A.M.); (J.M.H.)
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland
| | - Javier Benitez
- Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain;
- Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain;
| | - Anna González-Neira
- Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain;
| | - Christopher A. Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; (A.H.W.); (C.-C.T.); (C.A.H.)
| | - Thilo Dörk
- Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany; (T.D.); (N.V.B.)
| | - Natalia V. Bogdanova
- Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany; (T.D.); (N.V.B.)
- Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany
- NN Alexandrov Research Institute of Oncology and Medical Radiology, 223040 Minsk, Belarus
| | - Soo Hwang Teo
- Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya 47500, Malaysia;
- Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Nur Aishah Mohd Taib
- Breast Cancer Research Unit, University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia;
| | - Olivia Fletcher
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW7 3RP, UK; (O.F.); (N.J.)
| | - Nichola Johnson
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW7 3RP, UK; (O.F.); (N.J.)
| | - Mervi Grip
- Department of Surgery, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland;
| | - Robert Winqvist
- Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, 90570 Oulu, Finland;
- Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu 90570, Finland
| | - Carl Blomqvist
- Department of Oncology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland;
- Department of Oncology, Örebro University Hospital, 70185 Örebro, Sweden
| | - Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland;
| | - Annika Lindblom
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden;
- Department of Clinical Genetics, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Camilla Wendt
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 118 83 Stockholm, Sweden;
| | - Vessela N. Kristensen
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway; (V.N.K.); (NBCS Collaborators)
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
| | - NBCS Collaborators
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway; (V.N.K.); (NBCS Collaborators)
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Department of Research, Vestre Viken Hospital, 3004 Drammen, Norway
- Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0450 Oslo, Norway
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, 0450 Oslo, Norway
- Section for Breast- and Endocrine Surgery, Department of Cancer, Division of Surgery, Cancer and Transplantation Medicine, Oslo University Hospital-Ullevål, 0450 Oslo, Norway
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, 0450 Oslo, Norway
- Department of Pathology at Akershus University Hospital, 1478 Lørenskog, Norway
- Department of Oncology, Division of Surgery and Cancer and Transplantation Medicine, University Hospital-Radiumhospitalet, 0405 Oslo, Norway
- National Advisory Unit on Late Effects after Cancer Treatment, Department of Oncology, Oslo University Hospital, 0405 Oslo, Norway
- Department of Oncology, Akershus University Hospital, 1478 Lørenskog, Norway
- Oslo Breast Cancer Research Consortium, Oslo University Hospital, 0405 Oslo, Norway
| | - Rob A. E. M. Tollenaar
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
| | | | - Paolo Radice
- Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy;
| | - Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy;
| | - Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (U.H.); (M.M.)
| | - Mehdi Manoochehri
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (U.H.); (M.M.)
| | - James V. Lacey
- Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA 91010, USA;
- City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA
| | - Maria Elena Martinez
- Moores Cancer Center, University of California San Diego, La Jolla, CA 92037, USA;
- Herbert Wertheim School of Public Health and Longevity Science, University of California San Diego, La Jolla, CA 92161, USA
| | - Alison M. Dunning
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Paul D. P. Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK; (M.K.B.); (Q.W.); (J.D.); (K.M.); (P.D.P.P.); (D.F.E.)
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK; (M.K.B.); (Q.W.); (J.D.); (K.M.); (P.D.P.P.); (D.F.E.)
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; (M.S.); (D.M.C.); (P.A.H.); (R.M.); (A.M.D.)
| | - Keun-Young Yoo
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Daehee Kang
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; (J.P.); (S.C.); (S.K.P.); (D.K.)
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (W.H.); (D.-Y.N.)
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;
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Roberts SA, Carswell JM. Growth, growth potential, and influences on adult height in the transgender and gender-diverse population. Andrology 2021; 9:1679-1688. [PMID: 33969625 PMCID: PMC9135059 DOI: 10.1111/andr.13034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 05/03/2021] [Accepted: 05/03/2021] [Indexed: 12/30/2022]
Abstract
The sexually dimorphic trait of height is one aspect of the experience of transgender and gender‐diverse (TGD) individuals that may influence their gender dysphoria and satisfaction with their transition. In this article, we have reviewed the current knowledge of the factors that contribute to one's final adult height and how it might be affected in TGD youth who have not experienced their gonadal puberty in the setting of receiving gonadotropin‐releasing hormone analog (GnRHa) and gender‐affirming hormonal treatment. Additional research is needed to characterize the influence of growth and final adult height on the lived experience of TGD youth and adults and how to best assess their growth, predict their final adult height, and how medical transition can be potentially modified to help them meet their goals.
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Affiliation(s)
- Stephanie A Roberts
- Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.,Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Jeremi M Carswell
- Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.,Department of Pediatrics, Harvard Medical School, Boston, MA, USA
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23
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Kim OK, Yun JM, Lee M, Park SJ, Kim D, Oh DH, Kim HS, Lee J. Effects of a Mixture of Humulus japonicus on Longitudinal Bone Growth in Hypophysectomized Rats. J Med Food 2021; 24:497-504. [PMID: 34009019 DOI: 10.1089/jmf.2020.4876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Previously, we reported that the administration of a mixture of Humulus japonicus (MH) increased the longitudinal bone growth rate in Sprague Dawley rats. In this study, we investigated the effects of the dietary administration of MH on longitudinal bone growth in growth hormone (GH)-deficient hypophysectomized male and female rats to determine whether the effect of MH was similar to that of GH. We measured the nose-to-anus and nose-to-tail length gain, femur and tibia lengths, growth plate zones, and expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) after the dietary administration of MH or the injection of GH into hypophysectomized rats for 4 weeks. Results demonstrated that the dietary administration of MH had no effect on longitudinal bone growth, whereas the injection of GH increased the nose-to-tail length gain and femur and tibia lengths in hypophysectomized rats. In addition, MH did not affect the growth plate, bone mineralization, and expression of IGF-1 and IGFBP-3. These findings indicate that MH does not exert a GH-like effect and that the effects of MH and GH on longitudinal bone growth involve different pathways.
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Affiliation(s)
- Ok-Kyung Kim
- Division of Food and Nutrition and Human Ecology Research Institute, Chonnam National University, Gwangju, Korea
| | | | - Minhee Lee
- Department of Medical Nutrition, Kyung Hee University, Yongin, Korea
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul, Korea
| | - Soo-Jeung Park
- Department of Medical Nutrition, Kyung Hee University, Yongin, Korea
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul, Korea
| | | | - Dong Hwan Oh
- Department of Medical Nutrition, Kyung Hee University, Yongin, Korea
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul, Korea
| | | | - Jeongmin Lee
- Department of Medical Nutrition, Kyung Hee University, Yongin, Korea
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul, Korea
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24
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Küchler EC, de Lara RM, Omori MA, Marañón-Vásquez G, Baratto-Filho F, Nelson-Filho P, Stuani MBS, Blanck-Lubarsch M, Schroeder A, Proff P, Kirschneck C. Effects of estrogen deficiency during puberty on maxillary and mandibular growth and associated gene expression - an μCT study on rats. Head Face Med 2021; 17:14. [PMID: 33888144 PMCID: PMC8061017 DOI: 10.1186/s13005-021-00265-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 04/12/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Estrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology. Some studies support that estrogen is important for craniofacial growth and development. Therefore this in vivo animal study aimed to investigate, whether and in which way low estrogen levels in the prepubertal period affect craniofacial development in the postpubertal stage and to quantify the gene expression of RANK, RANKL and OPG in cranial growth sites in ovariectomized estrogen-deficient rats during puberty. METHODS Control (sham-operated, n = 18) and ovariectomy (OVX, n = 18) surgeries were performed on 21-days-old female Wistar rats. Animals euthanized at an age of 45 days (pubertal stage) were used for gene expression analyses (n = 6 per group) and immunohistochemistry of RANK, RANKL and OPG. Animals euthanized at 63 days of age (post-pubertal stage) were used for craniofacial two-dimensional and three-dimensional craniofacial measurements using μCT imaging (n = 12 per group). RESULTS In the μCT analysis of the mandible and maxilla many statistically significant differences between sham-operated and OVX groups were observed, such as increased maxillary and mandibular bone length in OVX animals (p < 0.05). Condylar volume was also significantly different between groups (p < 0.05). The sham-operated group showed a higher level of RANK expression in the midpalatal suture (p = 0.036) and the RANKL:OPG ratio levels were higher in the OVX group (p = 0.015). CONCLUSIONS Our results suggest that estrogen deficiency during the prepubertal period is associated with alterations in the maxillary and mandibular bone length and condylar growth.
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Affiliation(s)
- Erika Calvano Küchler
- Department of Orthodontics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. .,Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, Ribeirão Preto, SP, 14040-904, Brazil.
| | | | - Marjorie Ayumi Omori
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, Ribeirão Preto, SP, 14040-904, Brazil
| | - Guido Marañón-Vásquez
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, Ribeirão Preto, SP, 14040-904, Brazil
| | - Flares Baratto-Filho
- School of Dentistry, Univille University, R. Paulo Malschitzki, Joinville, SC, 89219-710, Brazil
| | - Paulo Nelson-Filho
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, Ribeirão Preto, SP, 14040-904, Brazil
| | - Maria Bernadete Sasso Stuani
- Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, Ribeirão Preto, SP, 14040-904, Brazil
| | - Moritz Blanck-Lubarsch
- Department of Orthodontics, University of Muenster, Albert-Schweitzer-Campus 1, Building W30, 48149, Münster, Germany
| | - Agnes Schroeder
- Department of Orthodontics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Peter Proff
- Department of Orthodontics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Christian Kirschneck
- Department of Orthodontics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
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25
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The NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty: Protocol and rationale for methods and measures. Neuroimage 2021; 234:117970. [PMID: 33771694 DOI: 10.1016/j.neuroimage.2021.117970] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/14/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023] Open
Abstract
Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children.
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26
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Kim JH, Lim JS. Early menarche and its consequence in Korean female: reducing fructose intake could be one solution. Clin Exp Pediatr 2021; 64:12-20. [PMID: 32403898 PMCID: PMC7806406 DOI: 10.3345/cep.2019.00353] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 12/27/2019] [Accepted: 02/28/2020] [Indexed: 12/31/2022] Open
Abstract
The mean age at menarche (AAM) of Korean females has been rapidly decreasing over the last 50 years; currently, the prevalence of early menarche (<12 years) is 22.3%. Female adolescents who experience early menarche are known to be at greater risk of psychosocial and behavioral problems along with several physical health problems such as menstrual problems. They also tend to achieve a shorter final height and develop obesity. Population-based Korean studies have shown a strong association between early menarche and the risk of obesity, insulin resistance, metabolic syndrome, nonalcoholic fatty liver disease, diabetes, breast cancer, and cardiovascular disease in adulthood. Although the exact mechanism of how early menarche causes cardiometabolic derangement in later adulthood is unknown, childhood obesity and insulin resistance might be major contributors. Recent studies demonstrated that an excessive consumption of fructose might underlie the development of obesity and insulin resistance along with an earlier AAM. A positive association was observed between sugar-sweetened beverages (a major source of fructose) intake and obesity, metabolic syndrome, insulin resistance, and cardiometabolic risk in Korean females. In pediatrics, establishing risk factors is important in preventing disease in later life. In this regard, early menarche is a simple and good marker for the management of cardiometabolic diseases in adulthood. Decreasing one's fructose intake might prevent early menarche as well as the development of obesity, insulin resistance, and cardiometabolic diseases.
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Affiliation(s)
- Ji Hyun Kim
- Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jung Sub Lim
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
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Kang BH, Cho JH, Kim SY, Jeong KA, Kim SH, Kim C, Lim SJ, Shim KS. Growth and Bone Mineral Density Changes in Ovariectomized Rats Treated with Estrogen Receptor Alpha or Beta Agonists. J Korean Med Sci 2020; 35:e370. [PMID: 33230983 PMCID: PMC7683238 DOI: 10.3346/jkms.2020.35.e370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 09/08/2020] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Estrogen controls the pubertal growth spurt, growth plate closure, and accretion of bone mineral density (BMD) of long bones after biding estrogen receptor (ER). There are two subtypes of ER, ERα and ERβ. If each ER subtype has different effects, we may control those actions by manipulating the estrogen binding intensity to each ER subtype and increase the final adult height without markedly reducing BMD or impairing reproductive functions. The purpose of our study was to compare these effects of ERα and ERβ on long bones in ovariectomized rats. METHODS Thirty female rats were ovariectomized and randomly divided into 3 groups. The control, propylpyrazole triol (PPT), and 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) groups were subcutaneously injected for 5 weeks with sesame oil, PPT as an ERα agonist, and DPN as an ERβ agonist, respectively. The crown-lump length and body weight were measured weekly. BMD, serum levels of growth hormone (GH) and estradiol were checked before and after 5 weeks of injections. Pituitary GH1 expression levels were determined with quantitative real-time polymerase chain reaction, the proximal tibias were dissected, decalcified and stained with hematoxylin-eosin, and the thicknesses of epiphyseal plates including proliferative and hypertrophic zones were measured in 20-evenly divided sites after 5 weeks of injections. Comparisons for auxological data, serum hormone and pituitary GH1 expression levels, BMD, and epiphyseal plate thicknesses among 3 groups before and after injections were conducted. RESULTS There was no significant difference in body lengths among 3 groups. The body weights were significantly lower, but, serum GH, pituitary GH1 expression levels, and BMDs were higher in PPT group than the other 2 groups after 5 weeks of injections. There was no significant difference in the thicknesses of the total epiphyseal plate, proliferative, and hypertrophic zone among 3 groups. CONCLUSION ERα is more involved in pituitary GH secretion and bone mineral deposition than ERβ. Weight gain might be prevented with the ERα agonist.
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Affiliation(s)
- Byung Ho Kang
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Ja Hyang Cho
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - So Youn Kim
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Kyoung A Jeong
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Shin Hee Kim
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Chanwoo Kim
- Department of Nuclear Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Sung Jig Lim
- Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Kye Shik Shim
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
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The role of postnatal estrogen deficiency on cranium dimensions. Clin Oral Investig 2020; 25:3249-3255. [PMID: 33099705 DOI: 10.1007/s00784-020-03655-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/20/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVES The aim of this study was investigate the cranium dimensions of adult female rats, who suffered estrogen deficiency during the prepubertal stage, to assess the impact of estrogen deficiency on craniofacial morphology. MATERIAL AND METHODS Twenty-two female Wistar rats were divided into ovariectomy (OVX) (n = 11) and sham-operated control (n = 11) groups. Bilateral ovariectomy were performed in both groups at 21 days old (prepubertal stage), and rats were euthanized at an age of 63 days (post-pubertal stage). Micro-CT scans were performed with rat skulls, and the cranium morphometric landmark measurements were taken in the dorsal, lateral, and ventral view positions. Differences in measurements between the OVX and sham control groups were assessed using t test with an established alpha error of 5%. RESULTS The measures of the rats' skull showed that the inter-zygomatic arch width and anterior cranial base length were significantly larger in OVX group (p = 0.020 and p = 0.050, respectively), whereas the length of parietal bone was significantly higher in the sham group (p = 0.026). For the remaining measurements no significant differences between groups were detected (p > 0.05). CONCLUSION This study provides evidence that ovariectomized rats had alterations in cranial bone dimensions, demonstrating that estrogens during puberty are important for skull morphology. CLINICAL RELEVANCE To understand the role of estrogen on the postnatal cranium development will impact the clinical diagnose and therapy during childhood and adolescence.
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Abstract
The growth plate is the cartilaginous portion of long bones where the longitudinal growth of the bone takes place. Its structure comprises chondrocytes suspended in a collagen matrix that go through several stages of maturation until they finally die, and are replaced by osteoblasts, osteoclasts, and lamellar bone.The process of endochondral ossification is coordinated by chondrocytes and a variety of humoral factors including growth hormone, parathyroid hormone, oestrogen, growth factors, cytokines, and various signalling pathways.Chondrocytes progress from a resting state to enter the phases of proliferation and hypertrophy. Under the influence of oestrogen, the proliferation of chondrocytes decreases as the resting chondrocytes are consumed. During the terminal phase of differentiation, cartilage is replaced by blood vessels and organized bone tissue, and once chondrocytes have died, the longitudinal growth of the bone ceases and the growth plate closes.The highly complex regulatory signals involved in this process are genetically determined, and genetic perturbations in any of the associated genes can result in abnormalities of bone growth. Hundreds of chondrodysplasias have been described, pointing to the complexity of the humoral control systems involved in endochondral ossification.While our knowledge of the mechanisms behind the various bone growth control systems is improving, a deeper understanding of the underlying processes could aid clinicians to better understand bone health and bone growth abnormalities. This review describes the current clinical research into the physiology of the growth plate. Cite this article: EFORT Open Rev 2020;5:498-507. DOI: 10.1302/2058-5241.5.190088.
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Affiliation(s)
- Yücel Ağırdil
- Department of Orthopaedics and Traumatology, İzzet Baysal State Hospital, Bolu, Turkey
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Tomé TDC, Quintana HT, Bortolin JA, Taffarel AA, Liberti EA, De Oliveira F. Extensive burn injury causes bone collagen network alteration and growth delay related to RANK-L immunoexpression change. Connect Tissue Res 2020; 61:465-474. [PMID: 31092061 DOI: 10.1080/03008207.2019.1620220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE Extensive burn injury mainly affects children, and hypermetabolic state can lead to growth delay. This study aimed to investigate bone histopathological and morphometric aspects, collagen fibers network and the immunoexpression of biological markers related to bone development in a young experimental model for extensive burn. MATERIALS AND METHODS A total of 28 male Wistar rats were distributed into Control (C) and subjected to scald burn injury (SBI) groups. Sham or injured animals were euthanized 4 or 14 days post-lesion and proximal epiphyses of the femur were submitted to histological, morphometric (thickness epiphyseal plate), and RUNX-2 and receptor activator of nuclear factor kappa- β ligand (RANK-L) immunoexpression methods. RESULTS Histopathological femoral findings showed delayed appearance of the secondary ossification center in SBI, 14 days post-injury. Collagen fibers 4 days after injury were observed in articular cartilage as a pantographic network with a transversally oriented lozenge-shaped mesh, but this network was thinner in SBI. Fourteen days after the injury, the pantographic network of collagen presented square-shaped mesh in C, but this aspect was changed to a wider mesh in SBI. Morphometric analysis of epiphyseal plate revealed that the SBI group had less thickness than the respective controls (p<0.05). RUNX-2 showed no difference between groups, but RANK-L score was higher in all SBI groups. CONCLUSIONS Extensive burn injury causes delayed bone growth and morphological changes. Alterations in collagen network and enhancement in immunoreactivity of RANK-L result in increased osteoclastogenesis.
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Affiliation(s)
- Tabata De Carvalho Tomé
- Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista , SP, Brazil
| | - Hananiah Tardivo Quintana
- Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista , SP, Brazil
| | - Jeferson André Bortolin
- Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista , SP, Brazil
| | - André Andriolli Taffarel
- Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista , SP, Brazil
| | | | - Flavia De Oliveira
- Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista , SP, Brazil
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Kim OK, Yun JM, Lee M, Park SJ, Kim D, Oh DH, Kim HS, Kim GY. A Mixture of Humulus japonicus Increases Longitudinal Bone Growth Rate in Sprague Dawley Rats. Nutrients 2020; 12:nu12092625. [PMID: 32872370 PMCID: PMC7551887 DOI: 10.3390/nu12092625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/24/2020] [Accepted: 08/27/2020] [Indexed: 01/10/2023] Open
Abstract
The aim of this study was to investigate the effects of administration of a mixture of Humulus japonicus (MH) on longitudinal bone growth in normal Sprague Dawley (SD) rats. We measured the femur and tibia length, growth plate area, proliferation of chondrocytes, and expression of insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3), and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) phosphorylation after dietary administration of MH in SD rats for four weeks. The nose–tail length gain and length of femur and tibia increased significantly in the group that received MH for a period of four weeks. We performed H&E staining and Bromodeoxyuridine/5-Bromo-2′-Deoxyuridine (BrdU) staining to examine the effect of dietary administration of MH on the growth plate and the proliferation of chondrocytes and found that MH stimulated the proliferation of chondrocytes and contributed to increased growth plate height during the process of longitudinal bone growth. In addition, serum levels of IGF-1 and IGFBP-3 and expression of IGF-1 and IGFBP-3 mRNAs in the liver and bone were increased, and phosphorylation of JAK2/STAT5 in the liver was increased in the MH groups. Based on these results, we suggest that the effect of MH on longitudinal bone growth is mediated by increased JAK2/STAT5-induced IGF-1 production.
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Affiliation(s)
- Ok-Kyung Kim
- Division of Food and Nutrition, Human Ecology Research Institute, Chonnam National University, Gwangju 61186, Korea;
| | - Jeong moon Yun
- PENS Co., Ltd., Seoul 07206, Korea; (J.m.Y.); (D.K.); (H.-S.K.)
| | - Minhee Lee
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul 02447, Korea; (M.L.); (S.-J.P.); (D.H.O.)
| | - Soo-Jeung Park
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul 02447, Korea; (M.L.); (S.-J.P.); (D.H.O.)
| | - Dakyung Kim
- PENS Co., Ltd., Seoul 07206, Korea; (J.m.Y.); (D.K.); (H.-S.K.)
| | - Dong Hwan Oh
- Research Institute of Clinical Nutrition, Kyung Hee University, Seoul 02447, Korea; (M.L.); (S.-J.P.); (D.H.O.)
| | - Hong-Sik Kim
- PENS Co., Ltd., Seoul 07206, Korea; (J.m.Y.); (D.K.); (H.-S.K.)
| | - Ga-Yeon Kim
- Department of Public Health, Dankook University Graduate School, Cheonan-si, Chungnam 31116, Korea
- Correspondence: ; Tel.: +82-41-550-1493
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Kurenkova AD, Medvedeva EV, Newton PT, Chagin AS. Niches for Skeletal Stem Cells of Mesenchymal Origin. Front Cell Dev Biol 2020; 8:592. [PMID: 32754592 PMCID: PMC7366157 DOI: 10.3389/fcell.2020.00592] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 06/17/2020] [Indexed: 12/16/2022] Open
Abstract
With very few exceptions, all adult tissues in mammals are maintained and can be renewed by stem cells that self-renew and generate the committed progeny required. These functions are regulated by a specific and in many ways unique microenvironment in stem cell niches. In most cases disruption of an adult stem cell niche leads to depletion of stem cells, followed by impairment of the ability of the tissue in question to maintain its functions. The presence of stem cells, often referred to as mesenchymal stem cells (MSCs) or multipotent bone marrow stromal cells (BMSCs), in the adult skeleton has long been realized. In recent years there has been exceptional progress in identifying and characterizing BMSCs in terms of their capacity to generate specific types of skeletal cells in vivo. Such BMSCs are often referred to as skeletal stem cells (SSCs) or skeletal stem and progenitor cells (SSPCs), with the latter term being used throughout this review. SSPCs have been detected in the bone marrow, periosteum, and growth plate and characterized in vivo on the basis of various genetic markers (i.e., Nestin, Leptin receptor, Gremlin1, Cathepsin-K, etc.). However, the niches in which these cells reside have received less attention. Here, we summarize the current scientific literature on stem cell niches for the SSPCs identified so far and discuss potential factors and environmental cues of importance in these niches in vivo. In this context we focus on (i) articular cartilage, (ii) growth plate cartilage, (iii) periosteum, (iv) the adult endosteal compartment, and (v) the developing endosteal compartment, in that order.
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Affiliation(s)
- Anastasiia D Kurenkova
- Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Ekaterina V Medvedeva
- Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Phillip T Newton
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Andrei S Chagin
- Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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Disorganization of chondrocyte columns in the growth plate does not aggravate experimental osteoarthritis in mice. Sci Rep 2020; 10:10745. [PMID: 32612184 PMCID: PMC7329885 DOI: 10.1038/s41598-020-67518-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 06/09/2020] [Indexed: 12/24/2022] Open
Abstract
Osteoarthritis (OA) is a multifactorial joint disease mainly affecting articular cartilage (AC) with a relevant biomechanical component. During endochondral ossification growth plate (GP) chondrocytes arrange in columns. GPs do not ossify in skeletally mature rodents. In neonatal mice, an altered joint loading induces GP chondrocyte disorganization. We aimed to study whether experimental OA involves GP disorganization in adult mice and to assess if it may have additional detrimental effects on AC damage. Knee OA was induced by destabilization of the medial meniscus (DMM) in wild-type (WT) adult mice, and in Tamoxifen-inducible Ellis-van-Creveld syndrome protein (Evc) knockouts (EvccKO), used as a model of GP disorganization due to Hedgehog signalling disruption. Chondrocyte column arrangement was assessed in the tibial GP and expressed as Column Index (CI). Both DMM-operated WT mice and non-operated-EvccKO showed a decreased CI, indicating GP chondrocyte column disarrangement, although in the latter, it was not associated to AC damage. The most severe GP chondrocyte disorganization occurred in DMM-EvccKO mice, in comparison to the other groups. However, this altered GP structure in DMM-EvccKO mice did not exacerbate AC damage. Further studies are needed to confirm the lack of interference of GP alterations on the analysis of AC employing OA mice.
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Papapanagiotou IK, Charamanta M, Roidi S, Al-Achmar NS, Soldatou A, Michala L. Letter to the Editor and Response. J Pediatr Adolesc Gynecol 2020; 33:316-317. [PMID: 32169401 DOI: 10.1016/j.jpag.2020.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Ioannis K Papapanagiotou
- First Department of Obstetrics and Gynaecology, National and Kapodistrian University of Athens, "Alexandra" General Hospital, Athens, Greece
| | - Maria Charamanta
- First Department of Obstetrics and Gynaecology, National and Kapodistrian University of Athens, "Alexandra" General Hospital, Athens, Greece
| | - Stella Roidi
- First Department of Obstetrics and Gynaecology, National and Kapodistrian University of Athens, "Alexandra" General Hospital, Athens, Greece
| | - Nikolaos Samer Al-Achmar
- First Department of Obstetrics and Gynaecology, National and Kapodistrian University of Athens, "Alexandra" General Hospital, Athens, Greece
| | - Alexandra Soldatou
- Second Department of Pediatrics, National and Kapodistrian University of Athens, Panagiotis and Aglaia Kyriakou Hospital, Athens, Greece
| | - Lina Michala
- First Department of Obstetrics and Gynaecology, National and Kapodistrian University of Athens, "Alexandra" General Hospital, Athens, Greece.
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Nasoori A. Formation, structure, and function of extra-skeletal bones in mammals. Biol Rev Camb Philos Soc 2020; 95:986-1019. [PMID: 32338826 DOI: 10.1111/brv.12597] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 03/07/2020] [Accepted: 03/17/2020] [Indexed: 12/12/2022]
Abstract
This review describes the formation, structure, and function of bony compartments in antlers, horns, ossicones, osteoderm and the os penis/os clitoris (collectively referred to herein as AHOOO structures) in extant mammals. AHOOOs are extra-skeletal bones that originate from subcutaneous (dermal) tissues in a wide variety of mammals, and this review elaborates on the co-development of the bone and skin in these structures. During foetal stages, primordial cells for the bony compartments arise in subcutaneous tissues. The epithelial-mesenchymal transition is assumed to play a key role in the differentiation of bone, cartilage, skin and other tissues in AHOOO structures. AHOOO ossification takes place after skeletal bone formation, and may depend on sexual maturity. Skin keratinization occurs in tandem with ossification and may be under the control of androgens. Both endochondral and intramembranous ossification participate in bony compartment formation. There is variation in gradients of density in different AHOOO structures. These gradients, which vary according to function and species, primarily reduce mechanical stress. Anchorage of AHOOOs to their surrounding tissues fortifies these structures and is accomplished by bone-bone fusion and Sharpey fibres. The presence of the integument is essential for the protection and function of the bony compartments. Three major functions can be attributed to AHOOOs: mechanical, visual, and thermoregulatory. This review provides the first extensive comparative description of the skeletal and integumentary systems of AHOOOs in a variety of mammals.
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Affiliation(s)
- Alireza Nasoori
- School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan
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Omori MA, Marañón‐Vásquez GA, Romualdo PC, Martins Neto EC, Stuani MBS, Matsumoto MAN, Nelson‐Filho P, Proff P, León JE, Kirschneck C, Küchler EC. Effect of ovariectomy on maxilla and mandible dimensions of female rats. Orthod Craniofac Res 2020; 23:342-350. [DOI: 10.1111/ocr.12376] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 03/12/2020] [Accepted: 03/20/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Marjorie Ayumi Omori
- Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Guido Artemio Marañón‐Vásquez
- Department of Pediatric Dentistry and Orthodontics School of Dentistry Federal University of Rio de Janeiro Rio de Janeiro Brazil
| | - Priscilla Coutinho Romualdo
- Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Evandro Carneiro Martins Neto
- Department of Oral & Maxillofacial Surgery, and Periodontology School of dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Maria Bernadete Sasso Stuani
- Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Mirian Aiko Nakane Matsumoto
- Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Paulo Nelson‐Filho
- Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Peter Proff
- Department of Orthodontics University Medical Centre of Regensburg Regensburg Germany
| | - Jorge Esquiche León
- Department of Stomatology, Public Health and Forensic Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
| | - Christian Kirschneck
- Department of Orthodontics University Medical Centre of Regensburg Regensburg Germany
| | - Erika C. Küchler
- Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto University of São Paulo Ribeirão Preto Brazil
- Department of Dentistry Universidade Positivo Curitiba Brazil
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Halcrow SE, Miller MJ, Snoddy AME, Fan W, Pechenkina K. Growing up different in Neolithic China: A contextualised case study and differential diagnosis of a young adult with skeletal dysplasia. INTERNATIONAL JOURNAL OF PALEOPATHOLOGY 2020; 28:6-19. [PMID: 31841791 DOI: 10.1016/j.ijpp.2019.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 10/16/2019] [Accepted: 11/03/2019] [Indexed: 06/10/2023]
Abstract
This paper presents a case study of a young adult from the late Neolithic Yangshao cultural period site (∼3300-2900 years BC) of Guanjia () located in Henan Province on the Central Plains of China, who has evidence for skeletal dysplasia characterised by proportional stunting of the long bones and a small axial skeleton, generalised osteopenia, and non-fusion of epiphyses. We provide a detailed differential diagnosis of skeletal dysplasia with paediatric onset and conclude that this is likely a form of hypopituitarism or hypothyroidism, an extremely rare finding within the archaeological context. This paper highlights the issues of distinguishing the forms of proportional dwarfism in palaeopathology because of the considerable variation in manifestation of these conditions. Finally, we assess whether there were any health and social implications for this person and community through the consideration of a bioarchaeology of care approach across the lifecourse, burial context, and information on social perceptions of 'difference' in the community. ：： （3300～2900）。，，，，。，，。。，。，、、""，。.
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Affiliation(s)
- Siân E Halcrow
- Department of Anatomy, University of Otago, New Zealand.
| | | | | | - Wenquan Fan
- Henan Provincial Institute of Cultural Relics and Archaeology, Zhengzhou, China
| | - Kate Pechenkina
- Department of Anthropology, Queens College, City University of New York, United States
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Vieira JS, Cunha EJ, de Souza JF, Chaves LHK, de Souza JL, Giovanini AF. Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate. World J Exp Med 2020; 10:1-9. [PMID: 31942441 PMCID: PMC6960019 DOI: 10.5493/wjem.v10.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 11/26/2019] [Accepted: 12/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone. Despite the abovementioned atractive reasons for alendronate’s use, few data on the effect of alendronate during epiphyseal growth exist.
AIM Verify the effect of alendronate on the growth epiphyseal plate, and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP2) in endochondral ossifing in specimens that have received alendronate.
METHODS Forty newborn rats were randomly divided into two groups: a control group (were given applications of 1 mg/kg physiologic saline) and a group that received Alendronate (a dose of 2.5 mg/kg). These groups were then divided into two subgroups for euthanasia in two and 12 d of life. After euthanasia, the femurs were removed, and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats. Posteriorly, the surgical pieces were also sent to the histopathology laboratory to produce histological slides. The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development. and other slides were immunohistochemically tested for anti- TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.
RESULTS On the third day, some diferences between the control group and specimens treated with alendronate were verified. Macroscopiccaly, we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate. On the 12th day, the bone size of the mice receiving the drug was significantly smaller than those of the control group. These results coincide with changes in the TGF-β1 and BMP-2 expression. In the specimens that received alendronate, the TGF-β1 was expressed in some sites of trabecular bone that was neoformed, peripherally to the bone marrow area. The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes. On the 12th day, all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate. In the interface between the trabecular bone and cartilage, an area of disorganized bone deposition was evident. Neoformed bone also appeared to be different at 12 d. In the control group, BMP-2 was positive in an intense area of bone trabeculae, whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.
CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously, a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.
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Postnatal skeletal growth is driven by the epiphyseal stem cell niche: potential implications to pediatrics. Pediatr Res 2020; 87:986-990. [PMID: 31830758 PMCID: PMC7196937 DOI: 10.1038/s41390-019-0722-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 10/31/2019] [Accepted: 12/03/2019] [Indexed: 12/23/2022]
Abstract
Children's longitudinal growth is facilitated by the activity of the growth plates, cartilage discs located near the ends of the long-bones. In order to elongate these bones, growth plates must continuously generate chondrocytes. Two recent studies have demonstrated that there are stem cells and a stem cell niche in the growth plate, which govern the generation of chondrocytes during the postnatal growth period. The niche, which allows stem cells to renew, appears at the same time as the secondary ossification center (SOC) matures into a bone epiphysis. Thus, the mechanism of chondrocyte generation differs substantially between neonatal and postnatal age, i.e., before and after the formation of the mineralized epiphyses. Hence, at the neonatal age bone growth is based on a consumption of chondro-progenitors whereas postnatally it is based on the activity of the stem cell niche. Here we discuss potential implications of these observations in relation to longitudinal growth, including the effects of estrogens, nutrition and growth hormone.
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40
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Kang S, Kim YM, Lee JA, Kim DH, Lim JS. Early Menarche is a Risk Factor for Short Stature in Young Korean Females: An Epidemiologic Study. J Clin Res Pediatr Endocrinol 2019; 11:234-239. [PMID: 30604602 PMCID: PMC6745461 DOI: 10.4274/jcrpe.galenos.2018.2018.0274] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE To assess the association between age at menarche and adult height [and body mass index (BMI)] in young Korean females and also to investigate whether early menarche (<12 years) is a risk factor for short stature and obesity in young Korean females. METHODS Data on 1148 females aged 18-30 years and 612 mother (612 pairs of mothers and daughters) from the 6th Korea National Health and Nutrition Examination Survey (2013-2015) were analyzed. RESULTS Among 1148 females, 256 (22.3%) had early menarche. Their stature was approximately 0.445 cm shorter when menarche had occurred one year earlier. The prevalence of short stature (≤153 cm) and obesity (BMI ≥25) was higher in females with early menarche compared to those with later menarche (short stature: 10.5% vs 6.4%, obesity; 20.7% vs 13.1%, all p<0.001). In multivariate regression, the odds ratio (OR) for short stature was 2.62 [95% confidence interval (CI): 1.26-5.44] after adjusting for current age and mother’s height. OR for obesity was 1.74 (95% CI: 0.98-3.07) after adjusting for age and maternal BMI. CONCLUSION Final height in girls is influenced by age of menarche. Early menarche increased the risk for adult short stature in young Korean females.
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Affiliation(s)
- Sol Kang
- Korea Cancer Center Hospital, Department of Pediatrics, Seoul, Republic of Korea
| | - Yoon Mo Kim
- Korea Cancer Center Hospital, Department of Pediatrics, Seoul, Republic of Korea
| | - Jun Ah Lee
- Korea Cancer Center Hospital, Department of Pediatrics, Seoul, Republic of Korea
| | - Dong Ho Kim
- Korea Cancer Center Hospital, Department of Pediatrics, Seoul, Republic of Korea
| | - Jung Sub Lim
- Korea Cancer Center Hospital, Department of Pediatrics, Seoul, Republic of Korea,* Address for Correspondence: Korea Cancer Center Hospital, Department of Pediatrics, Seoul, Republic of Korea Phone: +82-2-970-1224 E-mail:,
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41
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Clesham K, Piggott RP, Sheehan E. Displaced Salter-Harris I fracture of the distal ulna physis. BMJ Case Rep 2019; 12:12/8/e230783. [PMID: 31466954 DOI: 10.1136/bcr-2019-230783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 10-year-old girl presented to the emergency department having sustained a fall onto an outstretched left hand while playing soccer. Clinical and radiographical assessment identified a Salter-Harris I distal ulna fracture, as well as a buckle fracture of the distal radius. The injury was closed, and she had no neurovascular deficits on examination. She was brought to the operating theatre the following morning for closed reduction under general anaesthesia. Image intensification was used to confirm anatomical reduction, and an above-elbow moulded plaster-of-paris cast was applied. Follow-up clinical assessment at 6 weeks confirmed healing of the fracture, and she proceeded to make a full recovery. This case describes the anatomy and physiology of such rare injuries and outlines treatment principles and potential pitfalls based on best available evidence.
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Affiliation(s)
- Kevin Clesham
- Trauma and Orthopaedic Surgery, Midland Regional Hospital Tullamore, Co Offaly, Ireland
| | - Robert P Piggott
- Trauma and Orthopaedic Surgery, Midland Regional Hospital Tullamore, Co Offaly, Ireland
| | - Eoin Sheehan
- Trauma and Orthopaedic Surgery, Midland Regional Hospital Tullamore, Co Offaly, Ireland.,Trauma and Orthopaedic Surgery, University of Limerick, Limerick, Ireland
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42
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Mortzfeld BM, Taubenheim J, Klimovich AV, Fraune S, Rosenstiel P, Bosch TCG. Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways. Nat Commun 2019; 10:3257. [PMID: 31332174 PMCID: PMC6646324 DOI: 10.1038/s41467-019-11136-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 06/07/2019] [Indexed: 02/03/2023] Open
Abstract
How multicellular organisms assess and control their size is a fundamental question in biology, yet the molecular and genetic mechanisms that control organ or organism size remain largely unsolved. The freshwater polyp Hydra demonstrates a high capacity to adapt its body size to different temperatures. Here we identify the molecular mechanisms controlling this phenotypic plasticity and show that temperature-induced cell number changes are controlled by Wnt- and TGF-β signaling. Further we show that insulin-like peptide receptor (INSR) and forkhead box protein O (FoxO) are important genetic drivers of size determination controlling the same developmental regulators. Thus, environmental and genetic factors directly affect developmental mechanisms in which cell number is the strongest determinant of body size. These findings identify the basic mechanisms as to how size is regulated on an organismic level and how phenotypic plasticity is integrated into conserved developmental pathways in an evolutionary informative model organism.
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Affiliation(s)
- Benedikt M Mortzfeld
- Zoological Institute, Christian-Albrechts University Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany
- Department of Bioengineering, University of Massachusetts Dartmouth, 285 Old Westport Rd, Dartmouth, MA, 02747, USA
| | - Jan Taubenheim
- Zoological Institute, Christian-Albrechts University Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany
- Institute for Zoology and Organismic Interactions, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany
| | - Alexander V Klimovich
- Zoological Institute, Christian-Albrechts University Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany
| | - Sebastian Fraune
- Zoological Institute, Christian-Albrechts University Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany
- Institute for Zoology and Organismic Interactions, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian-Albrechts University Kiel, University Hospital Schleswig-Holstein, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany
| | - Thomas C G Bosch
- Zoological Institute, Christian-Albrechts University Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany.
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Risk Factors for Development of Canine and Human Osteosarcoma: A Comparative Review. Vet Sci 2019; 6:vetsci6020048. [PMID: 31130627 PMCID: PMC6631450 DOI: 10.3390/vetsci6020048] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 05/14/2019] [Accepted: 05/17/2019] [Indexed: 12/18/2022] Open
Abstract
Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; however, important species-specific differences are becoming increasingly recognized. In this review, we describe risk factors for the development of osteosarcoma in dogs and humans, including height and body size, genetics, and conditions that increase turnover of bone-forming cells, underscoring the concept that stochastic mutational events associated with cellular replication are likely to be the major molecular drivers of this disease. We also discuss adaptive, cancer-protective traits that have evolved in large, long-lived mammals, and how increasing size and longevity in the absence of natural selection can account for the elevated bone cancer risk in modern domestic dogs.
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Newton PT, Li L, Zhou B, Schweingruber C, Hovorakova M, Xie M, Sun X, Sandhow L, Artemov AV, Ivashkin E, Suter S, Dyachuk V, El Shahawy M, Gritli-Linde A, Bouderlique T, Petersen J, Mollbrink A, Lundeberg J, Enikolopov G, Qian H, Fried K, Kasper M, Hedlund E, Adameyko I, Sävendahl L, Chagin AS. A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate. Nature 2019; 567:234-238. [PMID: 30814736 DOI: 10.1038/s41586-019-0989-6] [Citation(s) in RCA: 141] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Accepted: 02/01/2019] [Indexed: 12/22/2022]
Abstract
Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification1. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth1,2, but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.
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Affiliation(s)
- Phillip T Newton
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. .,Department of Women's and Children's Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Stockholm, Sweden.
| | - Lei Li
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Baoyi Zhou
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | | | - Maria Hovorakova
- Department of Developmental Biology, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic
| | - Meng Xie
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Xiaoyan Sun
- Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Lakshmi Sandhow
- Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Artem V Artemov
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.,Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Evgeny Ivashkin
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Simon Suter
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Vyacheslav Dyachuk
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.,National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Vladivostok, Russian Federation
| | - Maha El Shahawy
- Department of Oral Biochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Amel Gritli-Linde
- Department of Oral Biochemistry, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Thibault Bouderlique
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Julian Petersen
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.,Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria
| | - Annelie Mollbrink
- Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Joakim Lundeberg
- Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Grigori Enikolopov
- Center for Developmental Genetics and Department of Anesthesiology, Stony Brook University, Stony Brook, NY, USA
| | - Hong Qian
- Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Kaj Fried
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Maria Kasper
- Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Eva Hedlund
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Igor Adameyko
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.,Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria
| | - Lars Sävendahl
- Department of Women's and Children's Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Stockholm, Sweden
| | - Andrei S Chagin
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. .,Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russian Federation.
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Cheng X, Li PZ, Wang G, Yan Y, Li K, Brand-Saberi B, Yang X. Microbiota-derived lipopolysaccharide retards chondrocyte hypertrophy in the growth plate through elevating Sox9 expression. J Cell Physiol 2018; 234:2593-2605. [PMID: 30264889 DOI: 10.1002/jcp.27025] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Accepted: 06/25/2018] [Indexed: 12/22/2022]
Abstract
Accumulating data show that the cytotoxicity of bacterial lipopolysaccharides (LPS) from microbiota or infection is associated with many disorders observed in the clinics. However, it is still obscure whether or not embryonic osteogenesis is affected by the LPS exposure during gestation. Using the early chicken embryo model, we could demonstrate that LPS exposure inhibits chondrogenesis of the 8-day chicken embryos by Alcian Blue-staining and osteogenesis of 17-day by Alcian Blue and Alizarin Red staining. Further analysis of the growth plates showed that the length of the proliferating zone (PZ) increases whereas that of the hypertrophic zone (HZ) decreased following LPS exposure. However there is no significant change on cell proliferation in the growth plates. Immunofluorescent staining, western blot analysis, and quantitive polymerase chain reaction revealed that Sox9 and Col2a1 are highly expressed at the messenger RNA level and their protein products are also abundant. LPS exposure causes a downregulation of Runx2 and Col10a1 expression in 8-day hindlimbs, and a suppression of Runx2, Col10a1, and Vegfa expression in 17-day phalanges. Knocking down Sox9 in ATDC5 cells by small interfering RNA transfection lead to the expression reduction of Col2a1, Runx2, and Col10a1, implying the vital role of Sox9 in the process of LPS-induced delay in the transition from proliferating chondrocytes to hypertrophic chondrocytes in the growth plate. In the presence of LPS, the antioxidant defense regulator nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is highly expressed, and the activities of superoxide dismutase 1 (SOD1), SOD2, and glutaredoxin rise in 17-day phalanges and ADTC5 cells. Simultaneously, an increase of intracellular ROS is observed. When Nrf2 expression was knocked down in ATDC5 cells, the expressions of Sox9, Col2a1, Runx2, Col10a1, and Vegfa were also going down as well. Taken together, our current data suggest that LPS exposure during gestation could restrict the chondrocytes conversion from proliferating to hypertrophic in the growth plate, in which LPS-induced Sox9 plays a crucial role to trigger the cascade of downstream genes by excessive ROS production and Nrf2 elevation.
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Affiliation(s)
- Xin Cheng
- Department of Histology and Embryology, International Joint Laboratory for Embryonic, Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.,Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China
| | - Pei-Zhi Li
- Department of Histology and Embryology, International Joint Laboratory for Embryonic, Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.,Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China
| | - Guang Wang
- Department of Histology and Embryology, International Joint Laboratory for Embryonic, Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.,Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China
| | - Yu Yan
- Department of Histology and Embryology, International Joint Laboratory for Embryonic, Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.,Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China
| | - Ke Li
- Department of Histology and Embryology, International Joint Laboratory for Embryonic, Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.,Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China
| | - Beate Brand-Saberi
- Department of Anatomy and Molecular Embryology, Ruhr-University Bochum, Bochum, Germany
| | - Xuesong Yang
- Department of Histology and Embryology, International Joint Laboratory for Embryonic, Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.,Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China
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Teerapornpuntakit J, Chanprapaph P, Charoenphandhu N. Previous Adolescent Pregnancy and Breastfeeding Does Not Negatively Affect Bone Mineral Density at the Age of Peak Bone Mass. Breastfeed Med 2018; 13:500-505. [PMID: 30156423 DOI: 10.1089/bfm.2018.0080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To determine bone mineral density (BMD) at the age of peak bone mass in women who previously experienced pregnancy and breastfeeding during adolescence. MATERIALS AND METHODS In this retrospective study, female volunteers aged 24-30 years who were pregnant during the age of 15-19 years and have had one to two babies were recruited. All of them experienced breastfeeding without history of bone- or calcium-related problems, such as fracture or low calcium intake. BMD was determined at the femur and L1-L4 spine by dual-energy X-ray absorptiometry. RESULTS We found that both volunteers who previously experienced breastfeeding and age-matched control volunteers had similar BMD at the L1-L4 spines and femora. Further analysis for site-specific changes of lumbar and femoral BMDs showed that the values of the breastfeeding group were not different from those of the control group except at L1 and L2, where BMD values were greater in breastfeeding group compared with the control group. At both femoral and vertebral sites, T- and Z-scores were apparently similar between the two groups. In addition, the BMD at peak bone mass had no significant correlation with breastfeeding duration. CONCLUSIONS Teenage pregnancy and breastfeeding did not negatively affect BMD later at the age of peak bone mass. Therefore, breastfeeding can be encouraged in teenage mothers.
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Affiliation(s)
- Jarinthorn Teerapornpuntakit
- 1 Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University , Bangkok, Thailand .,2 Department of Physiology, Faculty of Medical Science, Naresuan University , Phitsanulok, Thailand
| | - Pharuhas Chanprapaph
- 3 Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand
| | - Narattaphol Charoenphandhu
- 1 Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University , Bangkok, Thailand .,4 Department of Physiology, Faculty of Science, Mahidol University , Bangkok, Thailand .,5 Institute of Molecular Biosciences, Mahidol University , Nakhon Pathom, Thailand .,6 The Academy of Science , The Royal Society of Thailand, Dusit, Bangkok, Thailand
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Agostini G, Holt BM, Relethford JH. Bone functional adaptation does not erase neutral evolutionary information. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2018; 166:708-729. [DOI: 10.1002/ajpa.23460] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 02/26/2018] [Accepted: 03/01/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Gina Agostini
- Mayo Clinic/ASU Obesity Solutions, School of Human Evolution and Social ChangeArizona State UniversityTempe Arizona
| | - Brigitte M. Holt
- Department of AnthropologyUniversity of Massachusetts AmherstAmherst Massachusetts
| | - John H. Relethford
- Department of AnthropologyState University of New York at OneontaOneonta New York
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Kvernebo-Sunnergren K, Ankarberg-Lindgren C, Åkesson K, Andersson MX, Samuelsson L, Lovmar L, Dahlgren J. Hyperestrogenism Affects Adult Height Outcome in Growth Hormone Treated Boys With Silver-Russell Syndrome. Front Endocrinol (Lausanne) 2018; 9:780. [PMID: 30622515 PMCID: PMC6308318 DOI: 10.3389/fendo.2018.00780] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 12/11/2018] [Indexed: 11/29/2022] Open
Abstract
Background: Intrauterine growth retardation and short stature are common features in Silver-Russell syndrome (SRS). Despite recombinant growth hormone (rGH) treatment, poor pubertal height gain, affecting adult height (AH), is common. This study investigated whether growth patterns and estrogen concentrations are associated with AH outcome in rGH treated SRS males. Methods: In this retrospective longitudinal single-center study, 11 males with SRS were classified as non-responders (NR = 6) or responders (R = 5), depending on AH adjusted for midparental height. Epigenetic analysis and longitudinal growth measures, including bone age, rGH related parameters, pubertal development, gonadotropins and estrogen concentrations, were analyzed until AH. Results: Pubarche before 9 years was only observed in one NR. At 10 years of age, there was no difference in gonadotropins between NR and R. However, estradiol (E2) concentrations at 10 years of age showed a strong association to AH adjusted for MPH (r = -0.78, p < 0.001). Serum E2 (pmol/L) was significantly higher in NR at ages 10 years [median (range) 2 (<2-5) vs. <2 (<2)], 12 years [23 (10-57) vs. 2 (<2-2)] and 14 years [77 (54-87) vs. 24 (<2-38)] but not at 16 years. Birth weight standard deviation score (SDS) was lower in NR [-4.1 (-4.7 to -2.1) vs. -2.7 (-3.3 to -1.7)]. Weight gain (SDS) until pubertal onset was greater in NR [2.4 (1.4-3.5) vs. 0.8 (-0.4 to 1.7)] and pubertal height gain (SDS) was lower in NR [-1.0 (-2.7-0.4) vs. 0.1 (-0.1 to 1.1)]. At AH, a number of NR and R had high E2 concentrations and small testes. Conclusion: Increased E2 concentrations at age 10, 12, and 14 years were associated to less pubertal height gain, thus affecting AH. Due to the small number of patients, the results need to be confirmed in larger cohorts. The finding of impaired testicular development stresses the need of hormonal evaluation as a complement to clinical and radiological assessment when predicting AH in males with SRS.
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Affiliation(s)
- Kjersti Kvernebo-Sunnergren
- Department of Pediatrics, Ryhov County Hospital, Jönköping, Sweden
- Department of Pediatrics, Göteborg Pediatric Growth Research Center, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- *Correspondence: Kjersti Kvernebo-Sunnergren
| | - Carina Ankarberg-Lindgren
- Department of Pediatrics, Göteborg Pediatric Growth Research Center, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karin Åkesson
- Department of Pediatrics, Ryhov County Hospital, Jönköping, Sweden
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University Hospital, Linköping, Sweden
| | - Mats X. Andersson
- Department of Pediatrics, Göteborg Pediatric Growth Research Center, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden
| | - Lena Samuelsson
- Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Lovisa Lovmar
- Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jovanna Dahlgren
- Department of Pediatrics, Göteborg Pediatric Growth Research Center, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Brimacombe CS. The enigmatic relationship between epiphyseal fusion and bone development in primates. Evol Anthropol 2017; 26:325-335. [PMID: 29265660 DOI: 10.1002/evan.21559] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2017] [Indexed: 11/07/2022]
Abstract
Epiphyseal fusion in primates is a process that occurs in a regular sequence spanning a period of years and thus provides biological anthropologists with a useful marker of maturity that can be used to assess age and stage of development. Despite the many studies that have catalogued fusion timing and sequence pattern, comparatively little research has been devoted to understanding why these sequences exist in the first place. Answering this question is not necessarily intuitive; indeed, given that neither taxonomic affinities nor recent adaptations have been clearly defined, it is a challenge to explain this process in evolutionary terms. In all mammals, there is a tendency for the fusion of epiphyses at joints to occur close in sequence, and this has been proposed to relate to locomotor adaptations. Further consideration of the evidence suggests that linking locomotor behavior to sequence data alone is difficult to prove and may require a different type of evidence. Epiphyseal fusion should be considered in the context of other parameters that affect the developing skeleton, including how joint morphology relates to growth in length, as well as other possible morphological constraints. In recent years, developmental biology has been providing a better understanding of the molecular regulators of epiphyseal fusion. At some point in the near future, we may be able to link our understanding of the genetics of fusion timing to the possible selective mechanisms that are responsible for these sequences.
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Affiliation(s)
- Conrad Stephen Brimacombe
- Human Evolutionary Studies Program and Department of Archaeology, Simon Fraser University, Burnaby, BC, Canada
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Cho SM, Lee SH, Lee D, Lee JH, Chang GT, Kim H, Lee JY. The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:239. [PMID: 28464905 PMCID: PMC5414215 DOI: 10.1186/s12906-017-1651-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 02/23/2017] [Indexed: 02/07/2023]
Abstract
Background Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats. Methods Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 – 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry. Results There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8 ± 23.7 μm/day; P < 0.05) compared to the control group (498.0 ± 23.8 μm/day), while the 100 mg/kg YJT group exhibited a non-significant increase. The number of BrdU-positive cells in the chondrocytes of the rhGH-treated group exhibited a significant increase (103.8 ± 34.2 cells/mm2) compared to that of the control group (70.3 ± 19.7 cells/mm2), while the 300 mg/kg YJT group had a non-significant increase. Additionally, IGF-1 and BMP-2 were highly expressed in the growth plate in the 300 mg/kg YJT and rhGH groups. Conclusions YJT increased the longitudinal bone growth rate by stimulating chondrocyte proliferation with increasing increments of local IGF-1 and BMP-2 expression. Based on these findings, YJT may be a therapeutic candidate for the treatment of growth retardation during adolescence.
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