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Kiel M, Wuebker S, Remy M, Riemondy K, Smith F, Carey C, Williams T, Van Otterloo E. MEMO1 Is Required for Ameloblast Maturation and Functional Enamel Formation. J Dent Res 2023; 102:1261-1271. [PMID: 37475472 PMCID: PMC11066519 DOI: 10.1177/00220345231185758] [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] [Indexed: 07/22/2023] Open
Abstract
Coordinated mineralization of soft tissue is central to organismal form and function, while dysregulated mineralization underlies several human pathologies. Oral epithelial-derived ameloblasts are polarized, secretory cells responsible for generating enamel, the most mineralized substance in the human body. Defects in ameloblast development result in enamel anomalies, including amelogenesis imperfecta. Identifying proteins critical in ameloblast development can provide insight into specific pathologies associated with enamel-related disorders or, more broadly, mechanisms of mineralization. Previous studies identified a role for MEMO1 in bone mineralization; however, whether MEMO1 functions in the generation of additional mineralized structures remains unknown. Here, we identify a critical role for MEMO1 in enamel mineralization. First, we show that Memo1 is expressed in ameloblasts and, second, that its conditional deletion from ameloblasts results in enamel defects, characterized by a decline in mineral density and tooth integrity. Histology revealed that the mineralization defects in Memo1 mutant ameloblasts correlated with a disruption in ameloblast morphology. Finally, molecular profiling of ameloblasts and their progenitors in Memo1 oral epithelial mutants revealed a disruption to cytoskeletal-associated genes and a reduction in late-stage ameloblast markers, relative to controls. Collectively, our findings integrate MEMO1 into an emerging network of molecules important for ameloblast development and provide a system to further interrogate the relationship of cytoskeletal and amelogenesis-related defects.
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Affiliation(s)
- M. Kiel
- Iowa Institute for Oral Health Research, University of Iowa, College of Dentistry & Dental Clinics, Iowa City, IA, USA
- Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
| | - S. Wuebker
- Iowa Institute for Oral Health Research, University of Iowa, College of Dentistry & Dental Clinics, Iowa City, IA, USA
- Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
| | - M.T. Remy
- Iowa Institute for Oral Health Research, University of Iowa, College of Dentistry & Dental Clinics, Iowa City, IA, USA
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA
| | - K.A. Riemondy
- RNA Bioscience Initiative, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - F. Smith
- Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - C.M. Carey
- Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - T. Williams
- Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Children’s Hospital Colorado, Aurora, CO, USA
| | - E. Van Otterloo
- Iowa Institute for Oral Health Research, University of Iowa, College of Dentistry & Dental Clinics, Iowa City, IA, USA
- Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
- Department of Periodontics, University of Iowa, College of Dentistry & Dental Clinics, Iowa City, IA, USA
- The University of Iowa Craniofacial Anomalies Research Center, University of Iowa, Iowa City, IA, USA
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Shaffer IC, Nakano Y, Pham A, Short A, Nanci A, Zhang Y, Shemirani R, Den Besten PK. Effects of Early Life Adversity on Tooth Enamel Formation. FRONTIERS IN DENTAL MEDICINE 2022; 3. [PMID: 37034482 PMCID: PMC10079274 DOI: 10.3389/fdmed.2022.894753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
In a systemic effort to survive environmental stress, organ systems fluctuate and adapt to overcome external pressures. The evolutionary drive back toward homeostasis makes it difficult to determine if an organism experienced a toxic exposure to stress, especially in early prenatal and neonatal periods of development. Previous studies indicate that primary human teeth may provide historical records of experiences related to stressors during that early time window. To assess the molecular effects of early life adversity on enamel formation, we used a limited bedding and nesting (LBN) mouse model of early life adversity (ELA) to assess changes in the enamel organ gene expression and enamel matrix mineralization. On average, postnatal day 12 (P12) ELA mice weighed significantly less than the controls. When adjusted for animal weight, ELA molar enamel volume was reduced as compared with the controls, and the relative mineral density of molar enamel was significantly increased. There were no obvious changes in enamel matrix crystal morphology or structure in ELA as compared with the control mouse enamel. RNAseq showed extracellular matrix organization to be the most significantly affected GO and reactome pathways, whereas butanote metabolism was the most significantly altered KEGG pathway. Transcripts expressing the enamel matrix proteins amelogenin (Amelx) and enamelin (Enam) were among the top 4 most differentially expressed genes. When evaluating molecular mechanisms for the changes in gene expression in ELA enamel organs, we found significantly increased expression of Dlx3, while transcripts for clock genes Per1 and Nrd1 were downregulated. These findings support the possibility that the developing enamel organ is sensitive to the pressures of early life adversity and produces molecular and structural biomarkers reflecting these challenges.
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Affiliation(s)
- Ida C. Shaffer
- Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Yukiko Nakano
- Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Aidan Pham
- Departments of Pediatrics, Anatomy/Neurobiology, Neurology, University of California, Irvine, Irvine, CA, United States
| | - Annabel Short
- Departments of Pediatrics, Anatomy/Neurobiology, Neurology, University of California, Irvine, Irvine, CA, United States
| | - Antonio Nanci
- Department of Stomatology, Faculty of Dental Medicine, Université de Montréal, Montreal, QC, Canada
| | - Yan Zhang
- Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Rozana Shemirani
- Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Pamela K. Den Besten
- Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, United States
- Correspondence: Pamela K. Den Besten,
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IGFs in Dentin Formation and Regeneration: Progress and Remaining Challenges. Stem Cells Int 2022; 2022:3737346. [PMID: 35432548 PMCID: PMC9007658 DOI: 10.1155/2022/3737346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 02/27/2022] [Accepted: 03/19/2022] [Indexed: 02/06/2023] Open
Abstract
Tertiary dentin results from the interplay between the host defense and dental injury or infection. Modern endodontics aiming vital pulp treatment take the tertiary dentin formation as the interim step, with the final goal of a physiological pulp-dentin like tissue regeneration. Dental pulp stem cells have been nominated for contributing to differentiating into odontoblast-like cells who are responsible for reparative dentin formation. Understanding the original dentin formation mechanism provides us a blueprint while exploring the reparative dentin formation mechanism builds bridge to bonafide pulp-dentin tissue regeneration. Among all the regulators, growth factors have long been revealed under the spotlight. The insulin-like growth factor (IGF) family has been implicated in critical events of inducing dentin formation, which is essential for pulp treatment. The expression of IGF family members including IGF1, IGF1R, IGF2, and IGF2R has been well characterized in dental papilla cells, dental pulp stem cells, and periodontal ligament cells. Recent studies indicated IGF binding to the receptors activated pathways, including MAPK pathway, and AKT pathway, orchestrated proliferation, and differentiation, and finally, contributed to dentin formation. This review summarizes the role of IGF family in dentin formation during tooth development and tertiary dentin formation during dentin-pulp repair and sheds light on key parts of research for future treatment improvements.
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Zhang SY, Ren JY, Yang B. Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration. World J Stem Cells 2021; 13:1625-1646. [PMID: 34909115 PMCID: PMC8641023 DOI: 10.4252/wjsc.v13.i11.1625] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/14/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.
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Affiliation(s)
- Si-Yuan Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yin Ren
- Department of Oral Radiology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Yang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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The Role of GH/IGF Axis in Dento-Alveolar Complex from Development to Aging and Therapeutics: A Narrative Review. Cells 2021; 10:cells10051181. [PMID: 34066078 PMCID: PMC8150312 DOI: 10.3390/cells10051181] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/02/2021] [Accepted: 05/10/2021] [Indexed: 12/30/2022] Open
Abstract
The GH/IGF axis is a major regulator of bone formation and resorption and is essential to the achievement of normal skeleton growth and homeostasis. Beyond its key role in bone physiology, the GH/IGF axis has also major pleiotropic endocrine and autocrine/paracrine effects on mineralized tissues throughout life. This article aims to review the literature on GH, IGFs, IGF binding proteins, and their respective receptors in dental tissues, both epithelium (enamel) and mesenchyme (dentin, pulp, and tooth-supporting periodontium). The present review re-examines and refines the expression of the elements of the GH/IGF axis in oral tissues and their in vivo and in vitro mechanisms of action in different mineralizing cell types of the dento-alveolar complex including ameloblasts, odontoblasts, pulp cells, cementoblasts, periodontal ligament cells, and jaw osteoblasts focusing on cell-specific activities. Together, these data emphasize the determinant role of the GH/IGF axis in physiological and pathological development, morphometry, and aging of the teeth, the periodontium, and oral bones in humans, rodents, and other vertebrates. These advancements in oral biology have elicited an enormous interest among investigators to translate the fundamental discoveries on the GH/IGF axis into innovative strategies for targeted oral tissue therapies with local treatments, associated or not with materials, for orthodontics and the repair and regeneration of the dento-alveolar complex and oral bones.
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Moon JS, Nam YS, Kang JH, Yang DW, Kim DY, Lee SY, Ko HM, Kim MS, Kim SH. Regulatory role of insulin-like growth factor-binding proteins in odontogenic mineralization in rats. J Mol Histol 2021; 52:63-75. [PMID: 33141361 DOI: 10.1007/s10735-020-09923-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 10/23/2020] [Indexed: 12/14/2022]
Abstract
Much information is currently available for molecules in early odontogenesis, but there is limited knowledge regarding terminal cytodifferentiation of ameloblasts and odontoblasts for the determination of normal crown morphology. The present differential display PCR (DD-PCR) revealed that insulin-like growth factor-binding protein 5 (IGFBP5) was differentially expressed in molar tooth germs between the cap (before crown mineralization) and root formation (after crown mineralization) stages. Real-time PCR confirmed that the expression levels of IGFBP1-4 were not significantly changed but those of IGFBP5-7 were upregulated in a time-dependent manner. Immunoreactivities for IGFBP5-7 were hardly seen in molar germs at the cap/early bell stage and protective-stage ameloblasts at the root formation stage. However, the reactivity was strong in odontoblasts and maturation-stage ameloblasts, which are morphologically and functionally characterized by wide intercellular space and active enamel matrix mineralization. The localization of each IGFBP was temporospatial. IGFBP5 was localized in the nuclei of fully differentiated odontoblasts and ameloblasts, while IGFBP6 was localized in the apical cytoplasm of ameloblasts and odontoblasts with dentinal tubules, and IGFBP7 was mainly found in the whole cytoplasm of odontoblasts and the intercellular space of ameloblasts. IGFBP silencing using specific siRNAs upregulated representative genes for dentinogenesis and amelogenesis, such as DMP1 and amelogenin, respectively, and augmented the differentiation media-induced mineralization, which was confirmed by alizarin red s and alkaline phosphatase staining. These results suggest that IGFBP5-7 may play independent and redundant regulatory roles in late-stage odontogenesis by modulating the functional differentiation of ameloblasts and odontoblasts.
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Affiliation(s)
- Jung-Sun Moon
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Yoo-Sung Nam
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Jee-Hae Kang
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Dong-Wook Yang
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Dae-Yoon Kim
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Su-Young Lee
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Hyun-Mi Ko
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Min-Seok Kim
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea
| | - Sun-Hun Kim
- Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
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Regulation of IGF-I by IGFBP3 and IGFBP5 during odontoblast differentiation in mice. J Oral Biosci 2019; 61:157-162. [PMID: 31400542 DOI: 10.1016/j.job.2019.07.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 07/03/2019] [Accepted: 07/08/2019] [Indexed: 11/20/2022]
Abstract
OBJECTIVES Although intracellular signaling pathways of insulin-like growth factor I (IGF-I) related to the proliferation of dental pulp cells have been investigated, the switching mechanism from cell proliferation to differentiation during odontogenesis remains elusive. This study aimed to elucidate the role of IGF binding protein (IGFBP) 3 and 5 in regulation of IGF-I during odontoblast differentiation in mouse incisors. METHODS The detailed expression patterns of IGF-I, IGF-I receptor (IGF-IR), IGFBP3, and IGFBP5 together with that of an odontoblast differentiation marker, nestin, were examined by immunohistochemistry and/or in situ hybridization using paraffinized sections of TetOP-H2B-GFP mouse incisors at postnatal 4 weeks. RESULTS Undifferentiated dental papilla cells and preodontoblasts (preOB) showed intense IGF-I- and IGF-IRα-positive reactions, and the expression was observed in differentiated odontoblasts, such as immature odontoblasts (iOB) and mature odontoblasts (mOB). IGFBP3/Igfbp3 was transiently expressed in preOB and early iOB, and the intensity of expression gradually reduced with the progression of odontoblast differentiation. In contrast, immunohistochemical analysis for IGFBP5 identified a positive reaction in the undifferentiated dental papilla cells and differentiated odontoblasts, and the expression of Igfbp5 was reduced in the differentiated odontoblasts. CONCLUSION The present study demonstrated the expression patterns of IGF-I, IGF-IR, IGFBP3, and IGFBP5 during odontoblast differentiation in mouse incisors. These results suggested that IGFBP3 regulates the transition from the proliferative to differentiation stage by inhibiting the action of IGF-I on the proliferation of dental papilla cells, and that IGFBP5 plays an important role in the maintenance of the differentiated odontoblasts during tooth development.
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Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis. Sci Rep 2019; 9:368. [PMID: 30675004 PMCID: PMC6344556 DOI: 10.1038/s41598-018-36863-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 11/21/2018] [Indexed: 11/08/2022] Open
Abstract
Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells.
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Yan L, Sun S, Qu L. Insulin-like growth factor-1 promotes the proliferation and odontoblastic differentiation of human dental pulp cells under high glucose conditions. Int J Mol Med 2017; 40:1253-1260. [PMID: 28902344 DOI: 10.3892/ijmm.2017.3117] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 08/07/2017] [Indexed: 12/24/2022] Open
Abstract
Insulin-like growth factor-1 (IGF-1) promotes human dental pulp stem cell proliferation and osteogenic differentiation. However, the effects of IGF-1 on the proliferation, apoptosis and odontoblastic differentiation (mineralization) of dental pulp cells (DPCs) under high glucose (GLU) conditions remain unclear. In this study, isolated primary human DPCs were treated with various concentrations of high GLU. Cell proliferation and apoptosis were determined by Cell Counting Kit-8 and Annexin V-FITC/PI assays, respectively. The cells were cultured in odontoblastic induction medium containing various concentrations of high GLU. Odontoblastic differentiation was determined by alkaline phosphatase (ALP) activity assay. Mineralization formation was evaluated by von Kossa staining. The expression levels of IGF family members were measured by western blot analysis and RT-qPCR during proliferation and differentiation. The cells were then exposed to 25 mM GLU and various concentrations of IGF-1. Cell proliferation, apoptosis, ALP activity, mineralization formation and the levels of mineralization-related proteins were then evaluated. Our results revealed that high GLU significantly inhibited cell proliferation and promoted cell apoptosis. GLU (25 and 50 mM) markedly reduced ALP activity and mineralization on days 7 and 14 after differentiation. The levels of IGF family members were markedly decreased by high GLU during proliferation and differentiation. However, IGF-1 significantly reversed the effects of high GLU on cell proliferation and apoptosis. Additionally, IGF-1 markedly restored the reduction of ALP activity and mineralization induced by high GLU. Our findings thus indicate that IGF-1 attenuates the high GLU-induced inhibition of DPC proliferation, differentiation and mineralization.
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Affiliation(s)
- Lu Yan
- Department of Endodontics, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China
| | - Shangmin Sun
- Department of Periodontics, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China
| | - Liu Qu
- Department of Endodontics, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China
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Tao J, Zhai Y, Park H, Han J, Dong J, Xie M, Gu T, Lewi K, Ji F, Jia W. Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar. PLoS One 2016; 11:e0159946. [PMID: 27494172 PMCID: PMC4975438 DOI: 10.1371/journal.pone.0159946] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 07/11/2016] [Indexed: 12/16/2022] Open
Abstract
Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation.
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Affiliation(s)
- Jiang Tao
- Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Yue Zhai
- Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Hyun Park
- Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Junli Han
- Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Jianhui Dong
- Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Ming Xie
- Department of Prosthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Ting Gu
- Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Keidren Lewi
- Department of Medicine, Windsor University School of Medicine, St. Kitts & Nevis
| | - Fang Ji
- Department of Orthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
- * E-mail: (FJ); (WJ)
| | - William Jia
- Brain Research Centre, Department of Surgery, University of British Columbia, Canada
- * E-mail: (FJ); (WJ)
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Yamamoto T, Oida S, Inage T. Gene Expression and Localization of Insulin-like Growth Factors and Their Receptors throughout Amelogenesis in Rat Incisors. J Histochem Cytochem 2016; 54:243-52. [PMID: 16260589 DOI: 10.1369/jhc.5a6821.2005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Insulin-like growth factors (IGFs) are expressed in many tissues and control cell differentiation, proliferation, and apoptosis. In teeth, the temporo-spatial pattern of expression IGFs and their receptors has not been fully characterized. The purpose of this study was to obtain a comprehensive profile of their expression throughout the life cycle of ameloblasts, using the continuously erupting rat incisor model. Upper incisors of young male rats were fixed by perfusion, decalcified, and embedded in paraffin. Sections were processed for in situ hybridization and immunohistochemistry. mRNA and protein expression profiles IGF-I, IGF-II, IGF-IR, and IGF-IIR mRNA were essentially identical. At the apical loop of the incisor, very strong signals were seen in the outer enamel epithelium while the inner enamel epithelium showed a moderate reaction. In the region of ameloblasts facing pulp, inner enamel epithelium cells were still moderately reactive while signals over the outer enamel epithelium were slightly reduced. In the region of ameloblasts facing dentin and the initial portion of the secretory zone, signals in ameloblasts were weak while those over the outer enamel epithelium were strong. In the region of postsecretory transition, signals in both ameloblasts and papillary layer cells gradually increased. In maturation proper, signals in ameloblasts appeared as alternating bands of strong and weak reactivities, which corresponded to the regions of ruffle-ended and smooth-ended ameloblasts, respectively. Papillary layer cells also showed alternations in signal intensity that matched those in ameloblasts. These results suggest that the IGF family may act as an autocrine/paracrine system that influences not only cell differentiation but also the physiological activity of ameloblasts.
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Affiliation(s)
- Tatsuya Yamamoto
- Department of Anatomy, School of Dentistry, Nihon University, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, Japan.
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Kero D, Cigic L, Medvedec Mikic I, Galic T, Cubela M, Vukojevic K, Saraga-Babic M. Involvement of IGF-2, IGF-1R, IGF-2R and PTEN in development of human tooth germ - an immunohistochemical study. Organogenesis 2016; 12:152-167. [PMID: 27326759 DOI: 10.1080/15476278.2016.1197460] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Insulin-Like Growth Factor 2 (IGF-2) is a peptide hormone essential for prenatal growth and development. IGF-2 exerts its mitogenic effects via Insulin-Like Growth Factor 1 Receptor (IGF-1R), and is eliminated by binding to Insulin-Like Growth Receptor 2 (IGF-2R). IGF-2 is also negatively regulated by Phosphatase and Tensin Homolog (PTEN), a phosphatase mutated in various tumors. Not much is known about the interplay between these factors during human odontogenesis. In this study, expression patterns of IGF-2, IGF-1R, IGF-2R and PTEN were analyzed by double immunofluorescence in incisor human tooth germs during the foetal period of development between the 7th and 20th gestational week. Throughout the investigated period, IGF-2 was mostly expressed in enamel organ, whereas mild to moderate expression of PTEN could be seen in dental papilla and parts of enamel organ. Expression of IGF-1R was ubiquitous and displayed strong intensity throughout the entire enamel organ. In contrast, expression of IGF-2R had rather erratic pattern in enamel organ and dental papilla alike. Expression patterns of IGF-2, IGF-1R, IGF-2R and PTEN in highly proliferative cervical loops, as well as in differentiating pre-ameloblasts and pre-odontoblasts of cusp tip region during the early and late bell stages when enamel organ acquires definitive shape, indicate importance of these factors in crown morphogenesis of human incisor. Taken together, our data suggest the involvement of IGF-2, IGF-1R, IGF-2R and PTEN in temporo-spatial patterning of basic cellular processes (proliferation, differentiation) during normal tooth development. They are also relevant for improving knowledge of molecular basis of human odontogenesis.
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Affiliation(s)
- Darko Kero
- a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia
| | - Livia Cigic
- a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia
| | - Ivana Medvedec Mikic
- a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia
| | - Tea Galic
- a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia
| | - Mladen Cubela
- b Dental Clinic Cubela , KMV Humskog bb , Mostar , Bosnia and Herzegovina
| | - Katarina Vukojevic
- c Department of Anatomy, Histology and Embriology , School of Medicine, University of Split , Split , Croatia
| | - Mirna Saraga-Babic
- c Department of Anatomy, Histology and Embriology , School of Medicine, University of Split , Split , Croatia
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Expression of Thymosin β4 in Ameloblasts during Mouse Tooth Development. Appl Microsc 2016. [DOI: 10.9729/am.2016.46.1.58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Ida-Yonemochi H, Otsu K, Ohshima H, Harada H. The glycogen metabolism via Akt signaling is important for the secretion of enamel matrix in tooth development. Mech Dev 2016; 139:18-30. [PMID: 26809144 DOI: 10.1016/j.mod.2016.01.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 12/11/2015] [Accepted: 01/20/2016] [Indexed: 01/07/2023]
Abstract
Cells alter their energy metabolism depending on the stage of differentiation or various environments. In the ameloblast differentiation of continuous growing mouse incisors, we found temporary glycogen storage in preameloblasts before the start of enamel matrix secretion and investigated the relationship between enamel matrix secretion and glycogen metabolism. Immunohistochemistry showed that in the transitional stage from preameloblasts to secretory ameloblasts, the glycogen synthase changed from the inactive form to the active form, the expression of glycogen phosphorylase increased, and further, the levels of IGF-1, IGF-1 receptor and activated Akt increased. These results suggested that the activation of Akt signaling via IGF is linked to the onset of both glycogen metabolism and enamel matrix deposition. In the experiments using organ culture and ameloblast cell line, the activation of Akt signaling by IGF-1 stimulated glycogen metabolism through the up-regulation of Glut-1,-4 and Gsk-3β and the dephosphorylation of glycogen synthase. Subsequently, they resulted in increased enamel matrix secretion. In contrast, some inhibitors of Akt signals and glycogen synthesis/degradation down-regulated enamel matrix secretion. Taking these findings together, glycogen metabolism via Akt signaling is an essential system for the secretion of enamel matrix in ameloblast differentiation.
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Affiliation(s)
- Hiroko Ida-Yonemochi
- Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
| | - Keishi Otsu
- Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuda, Yahaba, Shiwa-gun, Iwate 028-3694, Japan.
| | - Hayato Ohshima
- Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
| | - Hidemitsu Harada
- Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuda, Yahaba, Shiwa-gun, Iwate 028-3694, Japan.
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Analysis of expression patterns of IGF-1, caspase-3 and HSP-70 in developing human tooth germs. Arch Oral Biol 2015; 60:1533-44. [PMID: 26276267 DOI: 10.1016/j.archoralbio.2015.07.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 06/26/2015] [Accepted: 07/06/2015] [Indexed: 11/23/2022]
Abstract
AIMS To analyze expression patterns of IGF-1, caspase-3 and HSP-70 in human incisor and canine tooth germs during the late bud, cap and bell stages of odontogenesis. MATERIALS AND METHODS Head areas or parts of jaw containing teeth from 10 human fetuses aged between 9th and 20th developmental weeks were immunohistochemically analyzed using IGF-1, active caspase-3 and HSP-70 markers. Semi-quantitative analysis of each marker's expression pattern was also performed. RESULTS During the analyzed period, IGF-1 and HSP-70 were mostly expressed in enamel organ. As development progressed, expression of IGF-1 and HSP-70 became more confined to differentiating tissues in the future cusp tip area, as well as in highly proliferating cervical loops. Few apoptotic bodies highly positive to active caspase-3 were observed in enamel organ and dental papilla from the cap stage onward. However, both enamel epithelia moderately expressed active caspase-3 throughout the investigated period. CONCLUSIONS Expression patterns of IGF-1, active caspase-3 and HSP-70 imply importance of these factors for early human tooth development. IGF-1 and HSP-70 have versatile functions in control of proliferation, differentiation and anti-apoptotic protection of epithelial parts of human enamel organ. Active caspase-3 is partially involved in formation and apoptotic removal of primary enamel knot, although present findings might reflect its ability to perform other non-death functions such as differentiation of hard dental tissues secreting cells and guidance of ingrowth of proliferating cervical loops.
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Li LW, Wong HM, Peng SM, McGrath CP. Anthropometric measurements and dental caries in children: a systematic review of longitudinal studies. Adv Nutr 2015; 6:52-63. [PMID: 25593143 PMCID: PMC4288280 DOI: 10.3945/an.114.006395] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
There is growing interest in the association between anthropometric measurements and dental caries in childhood over time (life-course studies). The aim of this review was to identify and systematically review the evidence of the association between anthropometric measurements and dental caries in childhood over time. PubMed, Institute for Scientific Information (ISI) Web of Knowledge, the Cochrane Library, and 6 other databases were searched to identify effective articles. A systematic approach involving critical appraisal was conducted to examine the relation between anthropometric measurements and dental caries in preschool- and school-aged populations from longitudinal studies. An initial search identified 1338 studies, with 59 potentially effective studies (κ = 0.82) and 17 effective studies (κ = 0.88). The quality of reporting among the studies ranged from 19.5 to 30.0 according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) criteria. Among the effective studies, 2 studies in which caries was used to predict anthropometric measurements consistently found an inverse association and 15 studies in which anthropometric measurements were used to predict caries were inconsistent, with results appearing to be influenced by nonuniformity of assessments, setting, and procedure of measurements; age and ethnicity of participants; and confounders of dental caries. In conclusion, among >1000 studies identified, 17 informed this systematic review. The quality of reporting of these studies varied considerably. Evidence of the association between anthropometric measurements and dental caries is conflicting and remains inconclusive.
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Affiliation(s)
| | | | | | - Colman P McGrath
- Periodontology and Public Health, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
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Kumakami-Sakano M, Otsu K, Fujiwara N, Harada H. Regulatory mechanisms of Hertwig׳s epithelial root sheath formation and anomaly correlated with root length. Exp Cell Res 2014; 325:78-82. [PMID: 24560742 DOI: 10.1016/j.yexcr.2014.02.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Accepted: 02/07/2014] [Indexed: 11/18/2022]
Abstract
Teeth are composed of two domains, the enamel-covered crown and cementum-covered root. The mechanism for determining the transition from crown to root is important for understanding root anomaly diseases. Hertwig׳s epithelial root sheath (HERS) is derived from the dental epithelium and is known to drive the growth of root dentin and periodontal tissue. Some clinical cases of hypoplastic tooth root are caused by the cessation of HERS development. Understanding the mechanisms of HERS development will contribute to the study of the disease and dental regenerative medicine. However, the developmental biology of tooth root formation has not been fully studied, particularly regarding HERS formation. Here, we describe the mechanisms of HERS formation on the basis of analysis of cell dynamics using imaging and summarize how the growth factor and its receptor regulate cell behavior of the dental epithelium.
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Affiliation(s)
- Mika Kumakami-Sakano
- Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Iwate 028-3694, Japan
| | - Keishi Otsu
- Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Iwate 028-3694, Japan
| | - Naoki Fujiwara
- Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Iwate 028-3694, Japan
| | - Hidemitsu Harada
- Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Iwate 028-3694, Japan.
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Gigante A, Brugè F, Cecconi S, Manzotti S, Littarru GP, Tiano L. Vitamin MK-7 enhances vitamin D3-induced osteogenesis in hMSCs: modulation of key effectors in mineralization and vascularization. J Tissue Eng Regen Med 2012; 9:691-701. [DOI: 10.1002/term.1627] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Revised: 07/28/2012] [Accepted: 08/28/2012] [Indexed: 11/06/2022]
Affiliation(s)
- A. Gigante
- Dipartimento di Scienze Cliniche e Molecolari; Università Politecnica delle Marche; Ancona Italy
| | - F. Brugè
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche; Università Politecnica delle Marche; Ancona Italy
| | - S. Cecconi
- Dipartimento di Scienze Cliniche e Molecolari; Università Politecnica delle Marche; Ancona Italy
| | - S. Manzotti
- Dipartimento di Scienze Cliniche e Molecolari; Università Politecnica delle Marche; Ancona Italy
| | - G. P. Littarru
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche; Università Politecnica delle Marche; Ancona Italy
| | - L. Tiano
- Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche; Università Politecnica delle Marche; Ancona Italy
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Kim KM, Lim J, Choi YA, Kim JY, Shin HI, Park EK. Gene expression profiling of oral epithelium during tooth development. Arch Oral Biol 2012; 57:1100-7. [DOI: 10.1016/j.archoralbio.2012.02.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Revised: 02/07/2012] [Accepted: 02/16/2012] [Indexed: 11/28/2022]
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Wang S, Mu J, Fan Z, Yu Y, Yan M, Lei G, Tang C, Wang Z, Zheng Y, Yu J, Zhang G. Insulin-like growth factor 1 can promote the osteogenic differentiation and osteogenesis of stem cells from apical papilla. Stem Cell Res 2012; 8:346-56. [PMID: 22286010 DOI: 10.1016/j.scr.2011.12.005] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Revised: 12/07/2011] [Accepted: 12/12/2011] [Indexed: 01/09/2023] Open
Abstract
Insulin-like growth factor 1 (IGF-1) plays an important role in the regulation of tooth root development, and stem cells from apical papilla (SCAPs) are responsible for the formation of root pulp and dentin. To date, it remains unclear whether IGF-1 can regulate the function of SCAPs. In this study, SCAPs were isolated and purified from human immature root apex, and stimulated by 100 ng/mL exogenous IGF-1. The effects of IGF-1 on the proliferation and differentiation of SCAPs were subsequently investigated. IGF-1 treated SCAPs presented the morphological and ultrastructural changes. Cell proliferation, alkaline phosphatase (ALP) activity and mineralization capacity of SCAPs were increased by IGF-1. Western blot and quantitative RT-PCR analyses further demonstrated that the expression of osteogenic-related proteins and genes (e.g., alkaline phosphatase, runt-related transcription factor 2, osterix, and osteocalcin) was significantly up-regulated in IGF-1 treated SCAPs, whereas the expression of odontoblast-specific markers (e.g., dentin sialoprotein and dentin sialophosphoprotein) was down-regulated by IGF-1. In vivo results revealed that IGF-1 treated SCAPs mostly gave birth to bone-like tissues while untreated SCAPs mainly generated dentin-pulp complex-like structures after transplantation. The present study revealed that IGF-1 can promote the osteogenic differentiation and osteogenesis capacity of SCAPs, but weaken their odontogenic differentiation and dentinogenesis capability, indicating that IGF-1 treated SCAPs can be used as a potential candidate for bone tissue engineering.
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Affiliation(s)
- Sainan Wang
- Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Effect of vitronectin bound to insulin-like growth factor-I and insulin-like growth factor binding protein-3 on porcine enamel organ-derived epithelial cells. Int J Dent 2012; 2012:386282. [PMID: 22567008 PMCID: PMC3332072 DOI: 10.1155/2012/386282] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2011] [Accepted: 01/17/2012] [Indexed: 11/17/2022] Open
Abstract
The aim of this paper was to determine whether the interaction between IGF, IGFBP, and VN modulates the functions of porcine EOE cells. Enamel organs from 6-month-old porcine third molars were dissociated into single epithelial cells and subcultured on culture dishes pretreated with VN, IGF-I, and IGFBP-3 (IGF-IGFBP-VN complex). The subcultured EOE cells retained their capacity for ameloblast-related gene expression, as shown by semiquantitative reverse transcription-polymerase chain reaction. Amelogenin expression was detected in the subcultured EOE cells by immunostaining. The subcultured EOE cells were then seeded onto collagen sponge scaffolds in combination with fresh dental mesenchymal cells and transplanted into athymic rats. After 4 weeks, enamel-dentin-like complex structures were present in the implanted constructs. These results show that EOE cells cultured on IGF-IGFBP-VN complex differentiated into ameloblasts-like cells that were able to secrete amelogenin proteins and form enamel-like tissues in vivo. Functional assays demonstrated that the IGF/IGFBP/VN complex significantly enhanced porcine EOE cell proliferation and tissue forming capacity for enamel. This is the first study to demonstrate a functional role of the IGF-IGFBP-VN complex in EOE cells. This application of the subculturing technique provides a foundation for further tooth-tissue engineering and for improving our understanding of ameloblast biology.
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Insulin-like growth factor 1 enhances the proliferation and osteogenic differentiation of human periodontal ligament stem cells via ERK and JNK MAPK pathways. Histochem Cell Biol 2012; 137:513-25. [PMID: 22227802 DOI: 10.1007/s00418-011-0908-x] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/26/2011] [Indexed: 12/14/2022]
Abstract
Insulin-like growth factor 1 (IGF-1) is a potent mitogenic protein which can enhance the osteogenic differentiation of periodontal ligament (PDL) fibroblasts. However, it remains unclear whether IGF-1 can stimulate the osteogenic differentiation and osteogenesis of human periodontal ligament stem cells (PDLSCs). In this study, STRO-1(+) PDLSCs were isolated from human PDL tissues, treated with IGF-1, and their osteogenic capacity was investigated in vitro and in vivo. Dimethyl-thiazol-diphenyl tetrazolium bromide assay and flow cytometry results demonstrated that 10-200 ng/mL IGF-1 can stimulate the proliferation ability of PDLSCs and 100 ng/mL is the optimal concentration. Exogenous IGF-1 can modify the ultrastructure, enhance the alkaline phosphatase activity, the mineralization ability of PDLSCs, and increase the expression of osteogenic markers (runt-related transcription factor 2, osterix, and osteocalcin) at mRNA and protein levels. In vivo transplantation illustrated that IGF-1 treated implants generated more mineralized tissues, and presented stronger expression of RUNX2, OSX, and OCN than control group. Moreover, the expression of phosphor-ERK and phosphor-JNK in these stem cells was upregulated by IGF-1, indicating that MAPK signaling pathway was activated during the osteogenic differentiation of PDLSCs mediated by IGF-1. Together, the results showed that IGF-1 can promote the osteogenic differentiation and osteogenesis of STRO-1(+) PDLSCs via ERK and JNK MAPK pathway, suggesting that IGF-1 is a potent agent for stem cell-based periodontal tissue regeneration.
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Matsumoto A, Harada H, Saito M, Taniguchi A. Induction of insulin-like growth factor 2 expression in a mesenchymal cell line co-cultured with an ameloblast cell line. In Vitro Cell Dev Biol Anim 2011; 47:675-80. [PMID: 21959847 PMCID: PMC3208818 DOI: 10.1007/s11626-011-9456-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2011] [Accepted: 09/09/2011] [Indexed: 11/30/2022]
Abstract
Various growth factors have been implicated in the regulation of cell proliferation and differentiation during tooth development. It has been unclear if insulin-like growth factors (IGFs) participate in the epithelium–mesenchyme interactions of tooth development. We previously produced three-dimensional sandwich co-culture systems (SW) containing a collagen membrane that induce the differentiation of epithelial cells. In the present study, we used the SW system to analyze the expression of IGFs and IGFRs. We demonstrate that IGF2 expression in mesenchymal cells was increased by SW. IGF1R transduces a signal; however, IGF2R does not transduce a signal. Recombinant IGF2 induces IGF1R and IGF2R expression in epithelial cells. IGF1R expression is increased by SW; however, IGF2R expression did not increase by SW. Thus, IGF2 signaling works effectively in SW. These results suggest that IGF signaling acts through the collagen membrane on the interaction between the epithelium and mesenchyme. In SW, other cytokines may be suppressed to induce IGF2R induction. Our results suggest that IGF2 may play a role in tooth differentiation.
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Affiliation(s)
- Asako Matsumoto
- Cell-Materials Interaction Group, Biomaterials Unit, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 Japan
- Biomaterials and Tissue Engineering, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572 Japan
- Kyokuto Pharmaceutical Industrial Co., Ltd., 3333-26 Aza-Asayama, Kamitezuna, Takahagi-shi, Ibaraki 318-0004 Japan
| | - Hidemitsu Harada
- Department of Oral Structure and Function Biology, Iwate Medical University, School of Dentistry, 1-3-27 Chuodori, Morioka, Iwate 020-8505 Japan
| | - Masahiro Saito
- Tissue Engineering Research Center, Tokyo University of Science, Noda, Chiba 278-8510 Japan
| | - Akiyoshi Taniguchi
- Cell-Materials Interaction Group, Biomaterials Unit, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 Japan
- Biomaterials and Tissue Engineering, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572 Japan
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Ren C, Diniz MG, Piazza C, Amm HM, Rollins DL, Rivera H, Devilliers P, Kestler DP, Waite PD, Mamaeva OA, Macdougall M. Differential enamel and osteogenic gene expression profiles in odontogenic tumors. Cells Tissues Organs 2011; 194:296-301. [PMID: 21597274 DOI: 10.1159/000324759] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Odontogenic tumors occur within the jaw bones and may be derived from odontogenic epithelium or ectomesenchyme or contain active components of both tissue types. We investigated the gene expression profile of enamel matrix proteins (EMPs), genes related to osteogenesis, and the mineralization process in odontogenic tumor cell populations focusing on an ameloblastoma (AB-1), a keratocystic odontogenic tumor (KCOT-1), and a calcifying epithelial odontogenic tumor (CEOT-1). All cell populations were shown to be epithelial in origin by CK14 expression. All tested EMPs were expressed by all odontogenic tumor cell types, with higher transcript levels seen in the AB-1 population especially for AMEL, AMBN, and ODAM. CEOT-1 cell populations showed a greater content of ALP-positive cells as well as higher ALP mRNA levels. Using qRT-PCR, we found a higher expression of 8 genes in the CEOT-1 compared to the AB-1 and KCOT-1. In this study we demonstrated the establishment of AB-1, KCOT-1 and CEOT-1 cell populations. The unique gene expression profiles of AB-1, KCOT-1, and CEOT-1 cells and their interactions with the surrounding microenvironment may support their unique tumor development, progression, and survival.
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Affiliation(s)
- C Ren
- Institute of Oral Health Research, University of Alabama at Birmingham School of Dentistry, Birmingham, AL, USA
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Kuo TF, Lin HC, Yang KC, Lin FH, Chen MH, Wu CC, Chang HH. Bone marrow combined with dental bud cells promotes tooth regeneration in miniature pig model. Artif Organs 2010; 35:113-21. [PMID: 21083830 DOI: 10.1111/j.1525-1594.2010.01064.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Growth factors and morphogens secreted by bone marrow mesenchymal stem cells (BMSCs) of bone marrow fluid may promote tooth regeneration. Accordingly, a tissue engineering approach was utilized to develop an economical strategy for obtaining the growth factors and morphogens from BMSCs. Unerupted second molar tooth buds harvested from miniature pigs were cultured in vitro to obtain dental bud cells (DBCs). Bone marrow fluid, which contains BMSCs, was collected from the porcine mandible before operation. DBCs suspended in bone marrow fluid were seeded into a gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer scaffold (GCHT scaffold). The DBCs/bone marrow fluid/GCHT scaffold was autografted into the original alveolar sockets of the pigs. Radiographic and histological examinations were applied to identify the structure of regenerated tooth at 40 weeks postimplantation. The present results showed that one pig developed a complete tooth with crown, root, pulp, enamel, dentin, odontoblast, cementum, blood vessel, and periodontal ligament in indiscriminate shape. Three animals had an unerupted tooth that expressed dentin matrix protein-1, vascular endothelial growth factor, and osteopontin; and two other pigs also had dental-like structure with dentin tubules. This study reveals that DBCs adding bone marrow fluid and a suitable scaffold can promote the tooth regeneration in autogenic cell transplantation.
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Affiliation(s)
- Tzong-Fu Kuo
- Institute of Veterinary Medicine, College of Veterinary Medicine, National Taiwan University, Taipei, Taiwan
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Matsumoto A, Harada H, Saito M, Taniguchi A. Induction of enamel matrix protein expression in an ameloblast cell line co-cultured with a mesenchymal cell line in vitro. In Vitro Cell Dev Biol Anim 2010; 47:39-44. [PMID: 21082283 DOI: 10.1007/s11626-010-9362-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2010] [Accepted: 10/19/2010] [Indexed: 11/29/2022]
Abstract
Interactions between epithelium and mesenchyme are important for organ and tissue development. In this study, in order to mimic interactions between epithelium and mesenchyme during native tooth development, we constructed three-dimensional culture systems in vitro using a collagen membrane. Two types of collagen membrane-based in vitro culture systems were constructed in which dental epithelial and dental follicle cell lines were cultured. One co-culture method involved inoculation of one cell line into one side of the collagen membrane, and the other cell line into the opposite side of the membrane (sandwich co-culture). As a control, the second method involved culture of one of the cell lines on a culture dish and the second cell line on a collagen membrane, facing away from the first cell line (separate co-culture). The HAT-7 cells were also grown as a monolayer culture on collagen. Ameloblast differentiation in these cultures was investigated by analysis of the mRNA and/or protein expression of ameloblastin and amelogenin. Our results suggest that interaction of epithelial and mesenchymal cells via the extracellular matrix is important for tooth differentiation in vitro. Our culture system should be a useful method for investigation of epithelial-mesenchymal interactions.
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Affiliation(s)
- Asako Matsumoto
- Advanced Medical Materials Group, Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, Japan
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Kay EJ, Northstone K, Ness A, Duncan K, Crean SJ. Is there a relationship between birthweight and subsequent growth on the development of dental caries at 5 years of age? A cohort study. Community Dent Oral Epidemiol 2010; 38:408-14. [PMID: 20545719 DOI: 10.1111/j.1600-0528.2010.00548.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To examine the associations between childhood growth and the presence of dental caries at age 5. METHODS Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) a population-based, prospective cohort study were used. We enrolled 14,541 pregnancies, and a 10% sample of these were dentally examined and measured at 61 months of age. Birthweight was obtained from medical records, and birth length and birthweight were assessed by trained ALSPAC measurers. A number of social and lifestyle factors were treated as potential confounding factors. RESULTS Of 985, children, 242 (24.6%) had caries at 61 months of age. After adjustment, increased weight at birth was associated with a small increased risk of caries at 61 months (OR: 1.08 (95% CI: 1.03, 1.13) per 100 g increase, P = 0.002). A similar association was noted with respect to increased length at birth. Current weight and height did not appear to be associated with caries risk. Children who had caries at 61 months had slower increases in weight and height between birth and 61 months than those without decay at 61 months. CONCLUSIONS The weak associations we have demonstrated between weight and length at birth and risk of caries at age 61 months cannot be considered causal, however, the relationship between the two variables warrants further investigation.
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Affiliation(s)
- Elizabeth Jane Kay
- Peninsula Dental School, Peninsula College of Medicine & Dentistry, Plymouth, UK.
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Catón J, Tucker AS. Current knowledge of tooth development: patterning and mineralization of the murine dentition. J Anat 2010; 214:502-15. [PMID: 19422427 DOI: 10.1111/j.1469-7580.2008.01014.x] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
The integument forms a number of different types of mineralized element, including dermal denticles, scutes, ganoid scales, elasmoid scales, fin rays and osteoderms found in certain fish, reptiles, amphibians and xenarthran mammals. To this list can be added teeth, which are far more widely represented and studied than any of the other mineralized elements mentioned above, and as such can be thought of as a model mineralized system. In recent years the focus for studies on tooth development has been the mouse, with a wealth of genetic information accrued and the availability of cutting edge techniques. It is the mouse dentition that this review will concentrate on. The development of the tooth will be followed, looking at what controls the shape of the tooth and how signals from the mesenchyme and epithelium interact to lead to formation of a molar or incisor. The number of teeth generated will then be investigated, looking at how tooth germ number can be reduced or increased by apoptosis, fusion of tooth germs, creation of new tooth germs, and the generation of additional teeth from existing tooth germs. The development of mineralized tissue will then be detailed, looking at how the asymmetrical deposition of enamel is controlled in the mouse incisor. The continued importance of epithelial-mesenchymal interactions at these later stages of tooth development will also be discussed. Tooth anomalies and human disorders have been well covered by recent reviews, therefore in this paper we wish to present a classical review of current knowledge of tooth development, fitting together data from a large number of recent research papers to draw general conclusions about tooth development.
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Affiliation(s)
- Javier Catón
- Department of Craniofacial Development and Orthodontics, King's College London, Guy's Hospital, UK
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Caviedes-Bucheli J, Canales-Sánchez P, Castrillón-Sarria N, Jovel-Garcia J, Alvarez-Vásquez J, Rivero C, Azuero-Holguín MM, Diaz E, Munoz HR. Expression of insulin-like growth factor-1 and proliferating cell nuclear antigen in human pulp cells of teeth with complete and incomplete root development. Int Endod J 2009; 42:686-93. [PMID: 19467045 DOI: 10.1111/j.1365-2591.2009.01568.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
AIM To quantify the expression of insulin-like growth factor-1 (IGF-1) and proliferating cell nuclear antigen (PCNA) in human pulp cells of teeth with complete or incomplete root development, to support the specific role of IGF-1 in cell proliferation during tooth development and pulp reparative processes. METHODOLOGY Twenty six pulp samples were obtained from freshly extracted human third molars, equally divided in two groups according to root development stage (complete or incomplete root development). All samples were processed and immunostained to determine the expression of IGF-1 and PCNA in pulp cells. Sections were observed with a light microscope at 80x and morphometric analyses were performed to calculate the area of PCNA and IGF-1 immunostaining using digital image software. Mann-Whitney's test was used to determine statistically significant differences between groups (P < 0.05) for each peptide and the co-expression of both. RESULTS Expression of IGF-1 and PCNA was observed in all human pulp samples with a statistically significant higher expression in cells of pulps having complete root development (P = 0.0009). CONCLUSION Insulin-like growth factor-1 and PCNA are expressed in human pulp cells, with a significant greater expression in pulp cells of teeth having complete root development.
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Affiliation(s)
- J Caviedes-Bucheli
- Postgraduate Endodontic Department, School of Dentistry, Pontificia Universidad Javeriana, Bogota, Colombia.
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Harada R, Watanabe K, Shirasu S, Kato M, Daito M. DNA microarray analysis of dental pulp fibroblasts exfoliated from deciduous teeth. PEDIATRIC DENTAL JOURNAL 2009. [DOI: 10.1016/s0917-2394(09)70151-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Lézot F, Thomas B, Greene SR, Hotton D, Yuan ZA, Castaneda B, Bolaños A, Depew M, Sharpe P, Gibson CW, Berdal A. Physiological implications of DLX homeoproteins in enamel formation. J Cell Physiol 2008; 216:688-97. [PMID: 18366088 DOI: 10.1002/jcp.21448] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Tooth development is a complex process including successive stages of initiation, morphogenesis, and histogenesis. The role of the Dlx family of homeobox genes during the early stages of tooth development has been widely analyzed, while little data has been reported on their role in dental histogenesis. The expression pattern of Dlx2 has been described in the mouse incisor; an inverse linear relationship exists between the level of Dlx2 expression and enamel thickness, suggesting a role for Dlx2 in regulation of ameloblast differentiation and activity. In vitro data have revealed that DLX homeoproteins are able to regulate the expression of matrix proteins such as osteocalcin. The aim of the present study was to analyze the expression and function of Dlx genes during amelogenesis. Analysis of Dlx2/LacZ transgenic reporter mice, Dlx2 and Dlx1/Dlx2 null mutant mice, identified spatial variations in Dlx2 expression within molar tooth germs and suggests a role for Dlx2 in the organization of preameloblastic cells as a palisade in the labial region of molars. Later, during the secretory and maturation stages of amelogenesis, the expression pattern in molars was found to be similar to that described in incisors. The expression patterns of the other Dlx genes were examined in incisors and compared to Dlx2. Within the ameloblasts Dlx3 and Dlx6 are expressed constantly throughout presecretory, secretory, and maturation stages; during the secretory phase when Dlx2 is transitorily switched off, Dlx1 expression is upregulated. These data suggest a role for DLX homeoproteins in the morphological control of enamel. Sequence analysis of the amelogenin gene promoter revealed five potential responsive elements for DLX proteins that are shown to be functional for DLX2. Regulation of amelogenin in ameloblasts may be one method by which DLX homeoproteins may control enamel formation. To conclude, this study establishes supplementary functions of Dlx family members during tooth development: the participation in establishment of dental epithelial functional organization and the control of enamel morphogenesis via regulation of amelogenin expression.
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Papagerakis P, Hu Y, Ye L, Feng JQ, Simmer JP, Hu JCC. Identifying promoter elements necessary for enamelin tissue-specific expression. Cells Tissues Organs 2008; 189:98-104. [PMID: 18703866 PMCID: PMC2754408 DOI: 10.1159/000151429] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Enamel development requires the strictly regulated spatiotemporal expression of genes encoding enamel matrix proteins. The mechanisms orchestrating the initiation and termination of gene transcription at each specific stage of amelogenesis are unknown. In this study, we identify cis- regulatory regions necessary for normal enamelin (Enam) expression. Sequence analysis of the Enam promoter 5'-noncoding region identified potentially important cis-regulatory elements located within 5.2 kb upstream of the Enam translation initiation site. DNA constructs containing 5.2 or 3.9 kb upstream of the Enam translation initiation site were linked to an LacZ reporter gene and used to generate transgenic mice. The 3.9-kb Enam-LacZ transgenic lines showed no expression in ameloblasts, but ectopic LacZ staining was detected in osteoblasts. In contrast, the 5.2-kb Enam-LacZ construct was sufficient to mimic the endogenous Enam ameloblast-specific expression pattern. Our study provides new insights into the molecular control of Enam cell- and stage-specific expression.
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Affiliation(s)
- Petros Papagerakis
- Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, Mich. 48108, USA.
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Hu Y, Papagerakis P, Ye L, Feng JQ, Simmer JP, Hu JCC. Distal cis-regulatory elements are required for tissue-specific expression of enamelin (Enam). Eur J Oral Sci 2008; 116:113-23. [PMID: 18353004 PMCID: PMC2701970 DOI: 10.1111/j.1600-0722.2007.00519.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Enamel formation is orchestrated by the sequential expression of genes encoding enamel matrix proteins; however, the mechanisms sustaining the spatio-temporal order of gene transcription during amelogenesis are poorly understood. The aim of this study was to characterize the cis-regulatory sequences necessary for normal expression of enamelin (Enam). Several enamelin transcription regulatory regions, showing high sequence homology among species, were identified. DNA constructs containing 5.2 or 3.9 kb regions upstream of the enamelin translation initiation site were linked to a LacZ reporter and used to generate transgenic mice. Only the 5.2-Enam-LacZ construct was sufficient to recapitulate the endogenous pattern of enamelin tooth-specific expression. The 3.9-Enam-LacZ transgenic lines showed no expression in dental cells, but ectopic beta-galactosidase activity was detected in osteoblasts. Potential transcription factor-binding sites were identified that may be important in controlling enamelin basal promoter activity and in conferring enamelin tissue-specific expression. Our study provides new insights into regulatory mechanisms governing enamelin expression.
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Affiliation(s)
- Yuanyuan Hu
- Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Petros Papagerakis
- Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Ling Ye
- Department of Biomedical Sciences, Baylor College of Dentistry, Dallas, TX, USA
| | - Jerry Q. Feng
- Department of Biomedical Sciences, Baylor College of Dentistry, Dallas, TX, USA
| | - James P. Simmer
- Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Jan C-C. Hu
- Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI, USA
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Caviedes-Bucheli J, Angel-Londoño P, Díaz-Perez A, Orozco MP, Álvarez JL, Lombana N, Díaz E, Muñoz HR. Variation in the Expression of Insulin-like Growth Factor-1 in Human Pulp Tissue According to the Root-development Stage. J Endod 2007; 33:1293-5. [DOI: 10.1016/j.joen.2007.07.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2007] [Revised: 07/12/2007] [Accepted: 07/18/2007] [Indexed: 10/22/2022]
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Hoeflich A, Götz W, Lichanska AM, Bielohuby M, Tönshoff B, Kiepe D. Effects of insulin-like growth factor binding proteins in bone -- a matter of cell and site. Arch Physiol Biochem 2007; 113:142-53. [PMID: 17922310 DOI: 10.1080/13813450701531193] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The actions of the insulin-like growth factor (IGF)-system are controlled by six IGF-binding proteins (IGFBPs). The IGFBPs are thought to affect local effects of IGF-I and IGF-II due to higher affinity if compared to IGF-I receptors and due to cell-type specific IGFBP expression patterns. It was found in IGFBP knockout models that the IGFBP family is functionally redundant. Thus, functional analysis of potential effects of IGFBPs is dependent on descriptive studies and models of IGFBP overexposure in vitro and in vivo. In the literature, the role of the IGFBPs for bone growth is highly controversial and, to date, no systematic look has been taken at IGFBPs resolving functional aspects of IGFBPs at levels of cell types and specific locations within bones. Since IGFBPs are thought to represent local modulators of the IGF actions and also exert IGF-independent effects, this approach is particularly reasonable on a physiological level. By sorting the huge number of in part controversial results on IGFBP effects in bone present in the literature for distinct cell types and bone sites it is possible to generate a focused, more specific and a less controversial picture of IGFBP functions in bone.
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Affiliation(s)
- A Hoeflich
- Laboratory of Mouse Genetics, Research Unit of Genetics and Biometry, Research Institute for the Biology of Farm Animals Dummerstorf (FBN), Germany.
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Christopher Dean M. Tooth microstructure tracks the pace of human life-history evolution. Proc Biol Sci 2007; 273:2799-808. [PMID: 17015331 PMCID: PMC1664636 DOI: 10.1098/rspb.2006.3583] [Citation(s) in RCA: 130] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
A number of fundamental milestones define the pace at which animals develop, mature, reproduce and age. These include the length of gestation, the age at weaning and at sexual maturity, the number of offspring produced over a lifetime and the length of life itself. Because a time-scale for dental development can be retrieved from the internal structure of teeth and many of these life-history variables tend to be highly correlated, we can discover more than might be imagined about fossil primates and more, in particular, about fossil hominids and our own evolutionary history. Some insights into the evolutionary processes underlying changes in dental development are emerging from a better understanding of the mechanisms controlling enamel and dentine formation. Our own 18-20-year period of growth and development probably evolved quite recently after ca 17 million years of a more ape-like life-history profile.
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Affiliation(s)
- M Christopher Dean
- Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
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Catón J, Bringas P, Zeichner-David M. Establishment and characterization of an immortomouse-derived odontoblast-like cell line to evaluate the effect of insulin-like growth factors on odontoblast differentiation. J Cell Biochem 2007; 100:450-63. [PMID: 16927272 DOI: 10.1002/jcb.21053] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Insulin-like growth factors (IGF-I and IGF-II) play important roles in regulating growth and differentiation of many different organs including teeth. The presence of these factors in the developing tooth has been demonstrated. In vitro studies using tooth explants grown in the presence of IGFs suggest that they promote differentiation of ameloblast and odontoblasts cells. This is achieved by inducing or repressing gene expression associated with these cells. Since some of the genes involved in tooth differentiation are expressed by both cells, to determine the effect of IGF on odontoblast cell differentiation we first need a cell line in which a controlled environment can be created. In this study, we report the establishment and characterization of an Immortomouse-derived odontoblast-like cell line. This conditional cell line can grow indefinitely under permissive conditions in the presence of INF-gamma at 33 degrees C, differentiate into odontoblast-like cells and produce a mineralized extracellular matrix when the INF-gamma is removed and cell maintained at 39 degrees C. Addition of exogenous IGFs to the media results in an accelerated production of a mineralized matrix. This is the result of increased transcription of genes associated with bone mineralization while down regulating genes associated with dentin formation like DSPP. This data suggest that IGFs induce dental papillae mesenchyme cells to produce a bone-like mineralized extracellular matrix.
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Affiliation(s)
- Javier Catón
- Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California 90033, USA
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Götz W, Heinen M, Lossdörfer S, Jäger A. Immunohistochemical localization of components of the insulin-like growth factor system in human permanent teeth. Arch Oral Biol 2006; 51:387-95. [PMID: 16321360 DOI: 10.1016/j.archoralbio.2005.10.005] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2005] [Revised: 09/06/2005] [Accepted: 10/12/2005] [Indexed: 10/25/2022]
Abstract
There is growing evidence that the insulin-like growth factor (IGF) system plays an important role in the biology of oro-dento-facial tissues and organs, including the development, homeostasis and regeneration of the periodontium. To obtain basic data on the occurrence and distribution of IGF components in human permanent teeth we immunohistochemically investigated 25 extracted, decalcified and paraffin-embedded teeth using mono and polyclonal antibodies against the ligands IGF-I and -II, the IGF1 receptor (IGF1R) and all six IGF binding proteins (IGFBP-1 to -6). In the extracellular matrix (ECM) of the adhering periodontal ligament (PDL), immunoreactivity for IGF-I, -II and IGFBP-1 and -6 was observed. PDL fibroblasts showed immunostaining for the IGF1R. For the cementum, in the acellular cementum only IGF-II could be detected, while outer cementum layers with inserting Sharpey's fibers reacted with all antibodies applied except for IGFBP-4 and -6. In the pulp, mainly fibrotic areas and areas around denticles were immunoreactive for IGF-I, IGFBP-1, -3, -5 and -6. Predentin and odontoblastic processes were stained for IGF-I and IGFBP-3. The spatially oriented occurrence of components of the IGF system in human permanent teeth indicates that specific functions of the IGFs may be localized in particular tissue compartments. In the cementum, several IGF components were found indicating roles in tissue homeostasis or attachment. The PDL may function as a reservoir for IGFs probably bound to ECM components. PDL fibroblasts could then respond in a paracrine manner. In the pulp, the IGF system may be involved in odontoblast biology, fibrosis and denticle formation.
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Affiliation(s)
- Werner Götz
- Department of Orthodontics, University of Bonn, Dental Clinic, Oral Biology Laboratory, Welschnonnenstr. 17, D-53111 Bonn, Germany.
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