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Jeon HH, Salas MCC, Park K, Fisher L, Ha S, Palmer C, Chan F, Graves DT. Comparison of the bone remodeling in the midpalatal suture during maxillary expansion between young and middle-aged mice. Bone 2025; 197:117512. [PMID: 40324615 DOI: 10.1016/j.bone.2025.117512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 04/17/2025] [Accepted: 05/02/2025] [Indexed: 05/07/2025]
Abstract
Maxillary expansion is a common orthodontic procedure for treating maxillary transverse deficiency. However, the cell responses to mechanical force may vary across different age groups, suggesting the need for age-specific treatment protocols. To compare the age-related responses to the mechanical force, we examined the 6-week- and 12-month-old mice undergoing maxillary expansion with 0.012-in. stainless steel orthodontic wire bonded to the maxillary first and second molars (25 g force). Mice were euthanized on days 0, 3, 7, and 14 for analysis. MicroCT analysis, tartrate-resistant acid phosphatase (TRAP) stain, and immunofluorescence/immunohistochemistry stain using antibodies to RUNX2, alkaline phosphatase (ALP), Gli1 and Ki67 along with the TUNEL assay, were conducted to evaluate suture width, osteoclast activity, new bone formation and mesenchymal stem cell (MSC) proliferation and apoptosis. Both 6-week- and 12-month-old mice exhibited successful midpalatal suture opening, but young mice demonstrated earlier and more intense osteoclast activity, along with higher expression of RUNX2 and ALP. Young mice also exhibited a higher percentage of Gli1+Ki67+ immunopositive cells, while middle-aged mice showed a higher percentage of Gli1+TUNEL+ positive cells on day 3 after maxillary expansion. Our findings suggest that aging negatively impacts mechanical force-induced bone remodeling by reducing osteoclastogenesis, osteogenesis, and MSC proliferation while increasing MSC apoptosis.
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Affiliation(s)
- Hyeran Helen Jeon
- Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Mary Cruz Contreras Salas
- Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Kyungjoon Park
- School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Lindsay Fisher
- School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sara Ha
- School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Caroline Palmer
- School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Fionna Chan
- School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Dana T Graves
- Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Othman SS, Saafan A, Al-Halbosiy MMF, Fathy I, Khursheed Alam M, El-Beialy AR, Al-Shmgani HS, Sulaiman GM. Ameliorating orthodontic relapse using laser bio-stimulation and mesenchymal stem cells in rats. J Genet Eng Biotechnol 2024; 22:100331. [PMID: 38494247 PMCID: PMC10980849 DOI: 10.1016/j.jgeb.2023.100331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
BACKGROUND Orthodontic relapse is a frequent problem that many patients experience. Although orthodontic therapy has advanced, recurrence rates can still reach 90%. We undertook a study to look at the possibilities of laser bio-stimulation and stem cells because they have showed promising outcomes in lowering recurrence rates. OBJECTIVES Our objective was to analyze the effects of Low-level laser therapy (LLLT) and Mesenchymal stem cells (MSC) alone and collectively on the rate of orthodontic relapse in rats radiographically and histologically. METHODS Rat maxillary central incisors were moved distally for two weeks. One week later, the incisors were retained. Animals (n = 40) were split into four groups. Control group (C); laser treatment Group (L), Bone marrow mesenchymal stem cells Group (BMSCs) and combination of Stem cells and laser-irradiation group (BMSCs-L). Removed retainer permitted relapse. Before stem cell application or laser irradiation, each animal underwent two CBCT scans. Rat maxillae were stained with Hx&E, Masson trichrome, and tartrate-resistant acid phosphatase antibody for histology, histochemistry, and immunohistochemistry. RESULTS AND CONCLUSIONS LLLT could reduce the relapse tendency, as shown by increased bone density and enhanced remodeling of hetero-formed periodontal ligament (PDL). Furthermore, the transfer of BMMSCs on the pressure side had positive effects on PDL remodeling and decreased, but did not inhibit, the relapse rate. Finally, the synergistic effects of the application of LLLT and BMMSC were better than the control but still moderate and long-lasting. CLINICAL SIGNIFICANCE Based on the improved relapse rate as proven in the present study, the Application of both LLLT and stem cells can be adopted to reduce the relapse tendency either lonely or collectively.
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Affiliation(s)
- Samer S Othman
- Department of Clinical Sciences, College of Dentistry, Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad, Iraq
| | - Ali Saafan
- Department of Medical Applications of Laser, National Institute for Laser Enhanced Sciences, Cairo University, Cairo, Egypt
| | | | - Iman Fathy
- Department of Oral Biology, Faculty of Dentistry, Ain Shams University, Cairo, Egypt
| | - Mohamed Khursheed Alam
- Professor of Orthodontics, Department of Preventive Dentistry, College of Dentistry, Jouf University, Sakakah, Saudi Arabia
| | - Amr R El-Beialy
- Department of Orthodontics and Dentofacial Orthopedics, Faculty of Dentistry, Cairo University, Cairo, Egypt.
| | - Hanady S Al-Shmgani
- Department of Biology, College of Education for Pure Sciences, Ibn Al-Haitham University of Baghdad, Baghdad 10066, Iraq.
| | - Ghassan M Sulaiman
- Division of Biotechnology, Department of Applied Sciences, University of Technology, Baghdad 10066, Iraq
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Li S, Wu Z, Ma Y, Zhu Y, Feng Z, Zhu Z, Qiu Y, Mao S. Differential Gene Expression Profiles and Pathways Highlight the Role of Osteoimmunology in Neurofibromatosis Type 1-Related Dystrophic Scoliosis With Osteopenia. Spine (Phila Pa 1976) 2023; 48:1588-1598. [PMID: 37614007 DOI: 10.1097/brs.0000000000004805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 08/10/2023] [Indexed: 08/25/2023]
Abstract
STUDY DESIGN Microarray approach and integrated gene network analysis. OBJECTIVE To explore the differential genetic expression profile, Gene Ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in human trabecular bone (HTB)-derived cells of dystrophic scoliosis secondary to neurofibromatosis type 1 (DS-NF1) and compare these to normal controls. SUMMARY OF BACKGROUND DATA The pathogenesis of DS-NF1 and the accompanying generalized osteopenia remain unclear. We hypothesized that HTBs may play a significant role in the etiology and pathogenesis of DS-NF1. MATERIALS AND METHODS Microarray analysis was used to identify differentially expressed genes of HTBs from patients with DS-NF1 compared with those from healthy individuals. Functional and pathway enrichment analysis were implemented through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway database. Then, the "search tool for the retrieval of interacting genes/proteins" database, Cytoscape, and "Molecular Complex Detection" were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Pathway enrichment analysis was further performed for hub genes and gene clusters identified through module analysis. Six potential crucial genes were selected for validation by reverse transcription polymerase chain reaction. RESULTS Bioinformatic analysis revealed that there are 401 previously unrecognized differentially expressed genes (238 up and 163 downregulated genes) in HTBs from patients with DS-NF1, and they were mainly enriched in terms of immune response, type-I interferon (IFN) signaling, TNF signaling pathway and etinoic acid inducible gene I-like receptor signaling pathway. Five hub genes, including signal transducer and activator of transcription 1, 2'-5'-oligoadenylate synthetase-like, IFN induced with helicase C domain 1, IFN regulatory factor 7, and MX dynamin-like GTPase 1 were identified through PPI network, which were mainly enriched in terms of Jak-STAT and etinoic acid inducible gene I-like receptor signaling pathway. An independently dysregulated protein cluster containing CCL2, CXCL1, CXCL3, CX3CL1, TLR1 , and CXCL12 was also identified through the PPI network. This indicated that the upper abnormally expressed genes may play essential roles in DS-NF1 pathogenesis and accompanied osteopenia. CONCLUSION Six key genes were identified in the progression of DS-NF1-related osteopenia. Immune response might play a key role in the progression of osteopenia, whereas a CXCL12 -mediated osteogenic effect might play a protective role.
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Affiliation(s)
- Song Li
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Chen H, Cai G, Ruan X, Lu Y, Li G, Chen Z, Guan Z, Zhang H, Sun W, Wang H. Bone-targeted bortezomib increases bone formation within Calvarial trans-sutural distraction osteogenesis. Bone 2023; 169:116677. [PMID: 36646264 DOI: 10.1016/j.bone.2023.116677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 01/01/2023] [Accepted: 01/10/2023] [Indexed: 01/14/2023]
Abstract
The high rate of relapse in craniofacial disharmony treatment via trans-sutural distraction osteogenesis (TSDO) is due to the failure to form a stable bone bridge in the suture gap. Bisphosphonates (BP) have a high propensity to localize to hydroxyapatite in the bone matrix and are commonly used as targeting ligands for local delivery of therapeutics into bone microenvironment. Bone-targeted Bortezomib (BP-Btz) is chemosynthetic by linking Btz (Bortezomib) to a BP residue and could target bone tissue to promote osteoblast differentiation and inhibit osteoclastogenesis. Here, suture-derived mesenchymal stem cells (SuSCs) and osteoclasts were treated with Btz and BP-Btz. Aforesaid drugs were injected locally into the sagittal sutures to explore their effects in TSDO. Further, pharmacological properties of BP-Btz in the suture expansion model were assessed by fluorescent BP analogs and levels of total ubiquitinated (Ub)-proteins. The results showed that BP-Btz could stimulate osteogenic differentiation of SuSCs, bind to bone matrix and inhibit osteoclastogenesis. Biological effects of BP-Btz were similar with those of Btz in osteoblast differentiation and osteoclastogenesis inhibition in vitro. Activated bone metabolism were detected after 14 days in the sagittal suture expansion model. Increased osteoid area, remarkably decreased osteoclast surface and enhanced osteogenesis were detected in vivo after treatment with BP-Btz. Green fluorescence signal detection and pharmacodynamic studies revealed that BP-Btz bound to suture edge, released Btz in remodeling conditions, had a higher local concentration and sustained longer than free Btz. This study delineated the clinical potential of bone-targeted Btz conjugate as an efficacious strategy to promote trans-sutural distraction osteogenesis.
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Affiliation(s)
- Hongyu Chen
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Guanhui Cai
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Xiaolei Ruan
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Yahui Lu
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Gen Li
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Zhenwei Chen
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Zhaolan Guan
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Hengwei Zhang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Wen Sun
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
| | - Hua Wang
- Jiangsu Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
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Ebadifar A, Eslamian L, Motamedian SR, Badiee MR, Mohaghegh S, Farahani M, Mohebbi Rad M, Mohammad-Rahimi H, Khojasteh A. Effect of mesenchymal stem cells with platelet-rich plasma carriers on bone formation after rapid maxillary expansion: An Animal Study. Orthod Craniofac Res 2022; 25:151-158. [PMID: 34273238 DOI: 10.1111/ocr.12518] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 07/08/2021] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To evaluate the effect of bone mesenchymal stem cells (BMSCs) with or without platelet-rich plasma (PRP) carriers on sutural new bone formation after rapid palatal expansion (RPE). SETTINGS AND SAMPLE POPULATION Sixty male Wistar rats were used in this study. MATERIAL AND METHODS All samples were subjected to 50cN of palatal expansion force for 7 days followed by 3 weeks of the retention period. The experimental groups received a single-dose injection of the specified solution at the time of retainer placement (BMSCs, PRP, BMSCs+PRP, normal saline). BMSCs used in this study were marked with the green fluorescent protein (GFP). New bone formation (NBF) in the sutural area was evaluated by µCT and occlusal radiography. In addition, semi-quantitative analyses were performed on histology images to analyse the quality of sutural bone, connective tissue and vascularization. Immunohistochemistry analyses were conducted for osteocalcin and collagen type I proteins. RESULTS After the 21-day retention period, limited GFP marked cells were detected around the sutural area. Samples treated with BMSCs + PRP had the highest NBF and showed higher expression of collagen type I and osteocalcin. CONCLUSION Injecting BMSCs + PRP may increase sutural bone density significantly. However, injecting BMSCs or PRP carriers alone did not affect sutural bone density.
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Affiliation(s)
- Asghar Ebadifar
- Dentofacial Deformities Research Center, Research Institute of Dental Sciences, & Department of orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ladan Eslamian
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Reza Motamedian
- Dentofacial Deformities Research Center, Research Institute of Dental Sciences, & Department of orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Badiee
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sadra Mohaghegh
- Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical Sciences
| | | | | | - Hossein Mohammad-Rahimi
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arash Khojasteh
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Liang W, Zhao E, Li G, Bi H, Zhao Z. Suture Cells in a Mechanical Stretching Niche: Critical Contributors to Trans-sutural Distraction Osteogenesis. Calcif Tissue Int 2022; 110:285-293. [PMID: 34802070 DOI: 10.1007/s00223-021-00927-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023]
Abstract
Trans-sutural distraction osteogenesis has been proposed as an alternative technique of craniofacial remodelling surgery for craniosynostosis correction. Many studies have defined the contribution of a series of biological events to distraction osteogenesis, such as changes in gene expression, changes in suture cell behaviour and changes in suture collagen fibre characteristics. However, few studies have elucidated the systematic molecular and cellular mechanisms of trans-sutural distraction osteogenesis, and no study has highlighted the contribution of cell-cell or cell-matrix interactions with respect to the whole expansion process to date. Therefore, it is difficult to translate largely primary mechanistic insights into clinical applications and optimize the clinical outcome of trans-sutural distraction osteogenesis. In this review, we carefully summarize in detail the literature related to the effects of mechanical stretching on osteoblasts, endothelial cells, fibroblasts, immune cells (macrophages and T cells), mesenchymal stem cells and collagen fibres in sutures during the distraction osteogenesis process. We also briefly review the contribution of cell-cell or cell-matrix interactions to bone regeneration at the osteogenic suture front from a comprehensive viewpoint.
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Affiliation(s)
- Wei Liang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, China
| | - Enzhe Zhao
- Department of Orthopedics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Guan Li
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, China
| | - Hongsen Bi
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, China.
| | - Zhenmin Zhao
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, China.
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Vali S, Khosravani S, Nobar BR, Motamedian SR. Rapid maxillary expansion supplementary methods: A scoping review of animal studies. Int Orthod 2022; 20:100614. [PMID: 35153159 DOI: 10.1016/j.ortho.2022.100614] [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: 10/24/2021] [Revised: 12/30/2021] [Accepted: 01/01/2022] [Indexed: 12/09/2022]
Abstract
INTRODUCTION Maxillary constriction is a relatively common condition. Various treatment modalities have been proposed for this condition such as rapid maxillary expansion (RME). Although RME can significantly expand the suture in a relatively short period of time, it has a number of drawbacks, mainly a lengthy retention period. The primary objective of this study was to assess the efficacy of the supplementary methods used in conjunction with RME for new bone formation (NBF) at the midpalatal suture (MPS). Relapse, bone healing, and root resorption were also studied as the secondary outcomes. MATERIALS AND METHODS The PubMed, Embase, and Cochrane library online databases were searched according to the PRISMA-ScR guideline. Animal studies on the effects of non-surgical supplementary methods other than laser therapy on NBF in RME were included and reviewed. RESULT Thirty-eight articles met the inclusion criteria. The supplementary methods were categorized into 6 groups: hormones, chemical agents, drugs, vitamins, proteins, and some other substances, which could not be assigned to any group. All the aforementioned substances enhanced NBF. Drugs such as bisphosphonates also increased bone resorption. The oestrogen hormone was shown to reduce treatment relapse. Lastly, stem cell application accelerated bone healing at the expanded MPS. CONCLUSION Administration of hormones, chemical agents, drugs, vitamins, herbs, and proteins may improve the outcomes of RME, shorten the retention period and consequently, reduce relapse in animals. However, the generalizability of these findings is limited due to the insubstantial number of studies published on each substance.
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Affiliation(s)
- Sara Vali
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sarvin Khosravani
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behrad Rahbani Nobar
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Reza Motamedian
- Dentofacial Deformities Research Center, Research Institute of Dental Sciences, and Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Yang Q, Zhou Y, Wang T, Cai P, Fu W, Wang J, Li X. MiRNA-1271-5p regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting forkhead box O1 (FOXO1). Cell Biol Int 2021; 45:1468-1476. [PMID: 33675274 DOI: 10.1002/cbin.11585] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/03/2021] [Accepted: 02/27/2021] [Indexed: 12/13/2022]
Abstract
Forkhead box O1 (FOXO1) is a key regulator of osteogenesis. The aim of this study was to identify the mechanisms of microRNAs (miRNAs) targeting FOXO1 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs). Three miRNA target prediction programs were used to search for potential miRNAs that target FOXO1. Quantitative real-time polymerase chain reaction was conducted to detect the expression of miR-1271-5p and FOXO1 during osteogenic differentiation. Target gene prediction and screening, luciferase reporter assay was used to verify the downstream target gene of miR-1271-5p. The expression levels of FOXO1 and Runx2 were detected by RT-qPCR and Western blot analysis. Alkaline phosphatase (ALP) activity and matrix mineralization were detected by biochemical methods. The expression levels of Runx2, ALP, and osteocalcin were detected by RT-qPCR. Our results showed that miR-1271-5p was downregulated during osteogenic induction. And the expression levels of miR-1271-5p were higher in osteoporotic tissues than that in adjacent nonosteoporotic tissues. The expression levels of FOXO1 were lower in osteoporotic tissues than that in adjacent nonosteoporotic tissues. And a negative correlation was found between miR-1271-5p and FOXO1 in osteoporotic tissues. Overexpression of miR-1271-5p downregulated FOXO1 and inhibited osteogenic differentiation in hMSCs. Overexpression of miR-1271-5p downregulated the expression of osteogenic markers and reduced ALP activity. In addition, ectopic expression of FOXO1 reversed the effect of miR-1271-5p on osteogenic differentiation. In conclusion, miR-1271-5p functioned as a therapeutic target of osteogenic differentiation in hMSCs by inhibiting FOXO1, which provides valuable insights into the use of miR-1271-5p as a target in the treatment of osteoporosis and other bone metabolic diseases.
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Affiliation(s)
- Qining Yang
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Yongwei Zhou
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Tianbao Wang
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Pengfei Cai
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Weicong Fu
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Jinhua Wang
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Xiaofei Li
- Department of Joint surgery, The affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
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Hassan MG, Zaher AR, Athanasiou AE. How orthodontic research can be enriched and advanced by the novel and promising evolutions in biomedicine. J Orthod 2021; 48:288-294. [PMID: 33860691 DOI: 10.1177/14653125211006116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Recent advances in developmental, molecular and cellular biology as well as biomedical technologies show a promising future for crossing the gap between biomedical basic sciences and clinical orthodontics. Orthodontic research shall utilise the advances and technologies in biomedical fields including genomics, molecular biology, bioinformatics and developmental biology. This review provides an update on the novel and promising evolutions in biomedicine and highlights their current and likely future implementation to orthodontic practice. Biotechnological opportunities in orthodontics and dentofacial orthopaedics are presented with regards to CRISPR technology, multi-omics sequencing, gene therapy, stem cells and regenerative medicine. Future orthodontic advances in terms of translational research are also discussed. Given the breadth of applications and the great number of questions that the presently available novel biomedical tools and techniques raise, their use may provide orthodontic research in the future with a great potential in understanding the aetiology of dentofacial deformities and malocclusions as well as in improving the practice of this clinical specialty.
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Affiliation(s)
- Mohamed G Hassan
- Department of Orthodontics, Faculty of Oral and Dental Medicine, South Valley University, Qena, Egypt
| | - Abbas R Zaher
- Department of Orthodontics, Faculty of Dentistry, Alexandria University, Alexandria, Egypt
| | - Athanasios E Athanasiou
- Department of Dentistry, School of Medicine, European University Cyprus, Nicosia, Cyprus.,Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
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Liang W, Ding P, Li G, Lu E, Zhao Z. Hydroxyapatite Nanoparticles Facilitate Osteoblast Differentiation and Bone Formation Within Sagittal Suture During Expansion in Rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:905-917. [PMID: 33688165 PMCID: PMC7936535 DOI: 10.2147/dddt.s299641] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 02/06/2021] [Indexed: 12/11/2022]
Abstract
Background The potential of relapse of craniofacial disharmony after trans-sutural distraction osteogenesis is high due to the failure to produce a stable bone bridge in the suture gap. The aim of this study is to evaluate whether hydroxyapatite nanoparticles (nHAP) have the effect of promoting osteoblast differentiation of suture-derived stem cells (SuSCs) and bone formation in sagittal suture during expansion. Methods SuSCs were isolated from sagittal sutures and exposed to various concentrations of nHAP (0, 25, 50, and 100 μg mL−1) to determine the optimal concentration of nHAP in osteoblast differentiation via performing Western Blotting and RT-qPCR. Twenty 4-week-old male Sprague–Dawley rats were randomly assigned into 4 groups: SHAM (sham-surgery), distraction, ACS (absorbable collagen sponge) and ACS+nHAP groups. In the ACS and ACS+nHAP groups, saline solution and nHAP suspended in a saline solution were delivered by ACS placed across the sagittal suture, respectively. In the latter three groups, the suture was expanded for 14 days by 50 g of constant force via a W shape expansion device. Suture gap area, bone volume fraction (BV/TV) and bone mineral density (BMD) of sagittal sutures were assessed via micro-CT, while the mechanical properties of sagittal sutures were evaluated via nanoindentation test. The efficacy of nHAP on bone formation in sagittal suture was also evaluated via BMP-2 immunohistochemistry staining. Results The expression of osteoblast related genes and proteins induced by 25μg mL−1 nHAP were significantly higher than the other groups in vitro (p<0.05). Furthermore, treating with 25μg mL−1 nHAP in vivo, the suture gap area was significantly reduced when compared with the distraction group. Correspondingly, the BV/TV, BMD, hardness and modulus of sagittal sutures were significantly increased in the ACS+nHAP group (p<0.05). Conclusion The 25μg mL−1 dose of nHAP delivered by ACS can facilitate bone formation into the sagittal suture during expansion via inducing osteoblast differentiation of SuSCs.
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Affiliation(s)
- Wei Liang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Pengbing Ding
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Guan Li
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Enhang Lu
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhenmin Zhao
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
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Liang W, Ding P, Li G, Lu E, Zhao Z. Hydroxyapatite Nanoparticles Facilitate Osteoblast Differentiation and Bone Formation Within Sagittal Suture During Expansion in Rats. Drug Des Devel Ther 2021; 15:905-917. [PMID: 33688165 PMCID: PMC8384124 DOI: 10.2147/dddt.s334630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 02/06/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The potential of relapse of craniofacial disharmony after trans-sutural distraction osteogenesis is high due to the failure to produce a stable bone bridge in the suture gap. The aim of this study is to evaluate whether hydroxyapatite nanoparticles (nHAP) have the effect of promoting osteoblast differentiation of suture-derived stem cells (SuSCs) and bone formation in sagittal suture during expansion. METHODS SuSCs were isolated from sagittal sutures and exposed to various concentrations of nHAP (0, 25, 50, and 100 μg mL-1) to determine the optimal concentration of nHAP in osteoblast differentiation via performing Western Blotting and RT-qPCR. Twenty 4-week-old male Sprague-Dawley rats were randomly assigned into 4 groups: SHAM (sham-surgery), distraction, ACS (absorbable collagen sponge) and ACS+nHAP groups. In the ACS and ACS+nHAP groups, saline solution and nHAP suspended in a saline solution were delivered by ACS placed across the sagittal suture, respectively. In the latter three groups, the suture was expanded for 14 days by 50 g of constant force via a W shape expansion device. Suture gap area, bone volume fraction (BV/TV) and bone mineral density (BMD) of sagittal sutures were assessed via micro-CT, while the mechanical properties of sagittal sutures were evaluated via nanoindentation test. The efficacy of nHAP on bone formation in sagittal suture was also evaluated via BMP-2 immunohistochemistry staining. RESULTS The expression of osteoblast related genes and proteins induced by 25μg mL-1 nHAP were significantly higher than the other groups in vitro (p<0.05). Furthermore, treating with 25μg mL-1 nHAP in vivo, the suture gap area was significantly reduced when compared with the distraction group. Correspondingly, the BV/TV, BMD, hardness and modulus of sagittal sutures were significantly increased in the ACS+nHAP group (p<0.05). CONCLUSION The 25μg mL-1 dose of nHAP delivered by ACS can facilitate bone formation into the sagittal suture during expansion via inducing osteoblast differentiation of SuSCs.
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Affiliation(s)
- Wei Liang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Pengbing Ding
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Guan Li
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Enhang Lu
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhenmin Zhao
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China
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12
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Mohaghegh S, Mohammad-Rahimi H, Eslamian L, Ebadifar A, Badiee MR, Farahani M, Mohebbi Rad M, Motamedian SR. Effect of mesenchymal stem cells injection and low-level laser therapy on bone formation after rapid maxillary expansion: an animal study. AMERICAN JOURNAL OF STEM CELLS 2020; 9:78-88. [PMID: 33489465 PMCID: PMC7811931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 12/07/2020] [Indexed: 06/12/2023]
Abstract
INTRODUCTION One of the most common orthodontic problems is maxillary constriction, which is mostly treated by rapid palatal expansion (RPE). However, its high rate of relapse and prolonged retention period have led to some challenges for orthodontists. To encounter these issues, accelerating bone regeneration can provide long-term stability of expanded maxilla. The present study aimed to evaluate the effect of low-level laser therapy (LLLT), bone marrow-derived mesenchymal stem cells (BMSCs) and their combination on promoting bone regeneration of the inter-maxillary suture after RPE in rats. MATERIALS AND METHOD Total of 60 rats went under RPE treatment. After 7 days, retention period started and interventions (group A, Control (saline); group B, LLLT; group C, BMSCs; group D, LLLT + BMSCs) were performed in the sutural area. After 21 days, radiographic and histological analyses were done. Histological analyses were conducted to evaluate the following criteria of the newly formed bone: the number of osteoblasts, new bone formation, vascularization, connective tissue. Moreover, sutural width was assessed in histologic images. To evaluate bone density at suture area, gray scale and Hounsfield Unit values were measured based on the occlusal radiographic and Micro-Computed topography images respectively. RESULTS Only in group C and D, osteoblasts and new bone formation were observed in all of the samples. There were no significant differences among the study groups regarding the post-treatment sutural width (P > 0.05). In the radiographic analysis, only group D showed more bone density compared to the control group (P = 0.022). Similarly, in micro-CT analysis, the most bone density was observed in group D which was significantly more than the control group (P = 0.013). CONCLUSION Our findings suggest that the application of LLLT and BMSCs is the most beneficial approach in accelerating bone regeneration in the inter-maxillary suture.
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Affiliation(s)
- Sadra Mohaghegh
- Undergraduate Student, Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical SciencesTehran, Iran
| | - Hossein Mohammad-Rahimi
- Dental Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical SciencesTehran, Iran
| | - Ladan Eslamian
- Professor of Orthodontics, Center of Research & Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical SciencesTehran, Iran
| | - Asghar Ebadifar
- Associated Professor of Orthodontics, Center of Research & Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical SciencesTehran, Iran
| | - Mohammad Reza Badiee
- Assistant Professor of Orthodontics, Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical SciencesTehran, Iran
| | | | - Masoud Mohebbi Rad
- Dental Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical SciencesTehran, Iran
| | - Saeed Reza Motamedian
- Assistant Professor of Orthodontics, Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical SciencesTehran, Iran
- Dentofacial Deformities Research Center, Research Institute of Dental Sciences, Shahid Beheshti University of Medical SciencesTehran, Iran
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Bhat M, Shetty P, Shetty S, Khan FA, Rahman S, Ragher M. Stem Cells and Their Application in Dentistry: A Review. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2019; 11:S82-S84. [PMID: 31198317 PMCID: PMC6555346 DOI: 10.4103/jpbs.jpbs_288_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The use of the term "stem cells" dates back to the 1800s; however, the application of the same is still not completely understood. Recent advances have indicated the harvesting of postnatal stem cells from sources such as the dental pulp and fat. The pluripotent nature of these cells allows for use in various aspects of treatment and patient care such as organ and tissue transplantation, bony defects repair, distraction osteogenesis, cell therapies, gene therapy, and toxicology testing of new drugs. This article explores the various aspects involved, the current status, and future challenges of stem cell therapy in patient care and management.
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Affiliation(s)
- Muraleedhara Bhat
- Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
| | - Praveen Shetty
- Department of Orthodontics, Srinivas Institute of Dental Sciences, Mangalore, Karnataka, India
| | - Subramanya Shetty
- Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
| | - Faizan A. Khan
- Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
| | - Shabeeb Rahman
- Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
| | - Mallikarjuna Ragher
- Department of Prosthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
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Gül Amuk N, Kurt G, Kartal Yandim M, Adan A, Baran Y. A minimally invasive transfer method of mesenchymal stem cells to the intact periodontal ligament of rat teeth: a preliminary study. Turk J Biol 2019; 42:382-391. [PMID: 30930622 PMCID: PMC6438122 DOI: 10.3906/biy-1712-62] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The aim of this study was to introduce a minimally invasive procedure for mesenchymal stem cell (MSC) transfer into the intact periodontal ligament (PDL) of the molar teeth in rats. Ten 12-week-old Wistar albino rats were used for this preliminary study. MSCs were obtained from bones of two animals and were labeled with green fluorescent protein (GFP). Four animals were randomly selected for MSC injection, while 4 animals served as a control group. Samples were prepared for histological analysis, Cox-2 mRNA expression polymerase chain reaction analysis, and fluorescent microscopy evaluation. The number of total cells, number of osteoclastic cells, and Cox-2 mRNA expression levels of the periodontal tissue of teeth were calculated. The number of total cells was increased with MSC injections in PDL significantly (P < 0.001). The number of osteoclastic cells and Cox-2 mRNA expression were found to be similar for the two groups. GFP-labeled MSCs were observed with an expected luminescence on the smear samples of the PDL with transferred MSCs. The results of this preliminary study demonstrate successful evidence of transferring MSCs to intact PDL in a nonsurgical way and offer a minimally invasive procedure for transfer of MSCs to periodontal tissues.
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Affiliation(s)
- Nisa Gül Amuk
- Department of Orthodontics, Faculty of Dentistry, Erciyes University , Kayseri , Turkey
| | - Gökmen Kurt
- Department of Orthodontics, Faculty of Dentistry, Bezmiâlem Vakıf University , İstanbul , Turkey
| | - Melis Kartal Yandim
- Department of Medical Biology, Faculty of Medicine, İzmir University of Economics , İzmir , Turkey
| | - Aysun Adan
- Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gül University , Kayseri , Turkey.,Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology , Urla, İzmir , Turkey
| | - Yusuf Baran
- Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology , Urla, İzmir , Turkey
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Li J, Wang X, Wang Y, Lu C, Zheng D, Zhang J. Isoquercitrin, a flavonoid glucoside, exerts a positive effect on osteogenesis in vitro and in vivo. Chem Biol Interact 2018; 297:85-94. [PMID: 30365939 DOI: 10.1016/j.cbi.2018.10.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Revised: 10/01/2018] [Accepted: 10/22/2018] [Indexed: 01/29/2023]
Abstract
Isoquercitrin (quercetin-3-O-β-d-glucopyranoside) possess various pharmacological effect as a biologically active compound. The aim of the present study was to investigate its potential effects on the proliferation and osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro and bone formation in the mid-palatal suture during rapid maxillary expansion (RME) in vivo. Cell proliferation of rat BMSCs was detected by cell-counting kit- 8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay and alizarin red staining were used to evaluate osteogenic differentiation of BMSCs. Furthermore, the expression levels of osteogenesis-related genes including runt-related transcription factor 2 (Runx2), bone sialoprotein (BSP) and activating transcription factor 6 (ATF6) were measured by real-time RT-PCR. In vivo, thirty-six male 6-week-old Wistar rats with or without suture expansion receive systemic administration of isoquercitrin or saline solution. Micro-CT, HE and Masson staining were used to compare the morphological changes between the groups. Bone morphogenetic protein 2 (BMP2) expression in the suture was detected using immunohistochemical staining. Our results showed that isoquercitrin significantly promoted cell proliferation, ALP activity and mineral deposition in the range from 0.01 to 1 μM. Moreover, the expression levels of Runx2, BSP and ATF6 were also upregulated. The measurement of micro-CT imaging and histological examinations demonstrated that daily oral administration of isoquercitrin (10 mg/kg) increased bone formation compared to the other groups. Furthermore, the expression level of BMP2 was also augmented in the presence of isoquercitrin. Consequently, those findings showed that isoquercitrin exerts stimulatory effects on osteogenesis in vitro and in vivo, suggesting that isoquercitrin could be a potential candidate for preventing relapse following RME within palatal sutures.
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Affiliation(s)
- Jing Li
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, China; Department of Orthodontics, School of Stomatology, Shandong University, Jinan, 250012, China
| | - Xuxia Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, China; Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, 250012, China
| | - Yingzi Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, China; Department of Orthodontics, School of Stomatology, Shandong University, Jinan, 250012, China
| | - Chengyan Lu
- Department of Stomatology, Zaozhuang Mining Group Central Hospital, Zaozhuang, 277800, China
| | - Dehua Zheng
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, China; Department of Orthodontics, School of Stomatology, Shandong University, Jinan, 250012, China
| | - Jun Zhang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, China; Department of Orthodontics, School of Stomatology, Shandong University, Jinan, 250012, China.
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Nugraha AP, Narmada IB, Ernawati DS, Dinaryanti A, Hendrianto E, Riawan W, Rantam FA. Bone alkaline phosphatase and osteocalcin expression of rat's Gingival mesenchymal stem cells cultured in platelet-rich fibrin for bone remodeling ( in vitro study). Eur J Dent 2018; 12:566-573. [PMID: 30369804 PMCID: PMC6178667 DOI: 10.4103/ejd.ejd_261_18] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE The aim of this study was to analyze the osteogenic differentiation of rat GMSCs cultured in PRF for bone remodeling. MATERIALS AND METHODS GMSCs were isolated from the lower gingival tissue of four healthy, 250 g, 1-month old, male rats (Rattus norvegicus) cut into small fragments, cultured for 2 weeks, and subsequently passaged every 4-5 days. GMSCs isolated in passage 3 were characterized by CD34, CD45, CD44, CD73, CD90, and CD105 using fluorescein isothiocyanate immunocytochemistry (ICC) examination. GMSCs in passage 3-5 cultured in five M24 plates (N = 108; n = 6/group) for 7, 14, and 21 days with three different mediums as follows: Control (-) group: α-Modified Eagle Medium; Control (+) group: High-dose glucose Dulbecco's Modified Eagle's Medium (DMEM-HG) + osteogenic medium; and treatment group: DMEM-HG + osteogenic medium + PRF. GMSCs were osteogenic differentiation cultured in vitro in three different mediums by bone alkaline phosphatase (BALP) and osteocalcin (OSC) marker using ICC monoclonal antibody. STATISTICAL ANALYSIS USED The one-way analysis of variance was performed (P < 0.05) based on Shapiro-Wilk and Levene's tests (P > 0.05). RESULTS GMSCs were shown to present + CD44, +CD73, +CD90, +CD105 and - CD34, - and CD45 expression as MSCs markers. The treatment group showed the highest BALP expression (16.00 ± 1.732) on day 7, while OSC expression (13.67 ± 2.309) on day 21 showed the statistically significant difference between groups (P < 0.05). CONCLUSION GMSCs cultured in PRF demonstrated potential osteogenic differentiation ability capable of accelerating in vitro bone remodeling by enhancing BALP and OSC expression.
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Affiliation(s)
- Alexander Patera Nugraha
- Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Doctoral Student of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
| | - Ida Bagus Narmada
- Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Diah Savitri Ernawati
- Department of Oral Medicine Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Aristika Dinaryanti
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
| | - Eryk Hendrianto
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
| | - Wibi Riawan
- Department of Biochemistry and Molecular, Biochemistry Biomolecular Laboratory, Faculty of Medicine, Universitas Brawijaya, Surabaya, Indonesia
| | - Fedik Abdul Rantam
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia
- Department of Microbiology, Virology and Immunology Laboratory, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
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Nugraha AP, Narmada IB, Ernawati DS, Dinaryanti A, Hendrianto E, Ihsan IS, Riawan W, Rantam FA. Osteogenic potential of gingival stromal progenitor cells cultured in platelet rich fibrin is predicted by core-binding factor subunit-α1/Sox9 expression ratio ( in vitro). F1000Res 2018; 7:1134. [PMID: 30430007 PMCID: PMC6097418 DOI: 10.12688/f1000research.15423.1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/10/2018] [Indexed: 12/16/2022] Open
Abstract
Background: Alveolar bone defect regeneration has long been problematic in the field of dentistry. Gingival stromal progenitor cells (GSPCs) offer a promising solution for alveolar bone regeneration. In order to optimally differentiate and proliferate progenitor cells, growth factors (GFs) are required. Platelet rich fibrin (PRF) has many GFs and can be easily manufactured. Core-binding factor subunit-α1 (CBF-α1) constitutes a well-known osteogenic differentiation transcription factor in SPCs. Sox9, as a chondrogenic transcription factor, interacts and inhibits CBF-α1, but its precise role in direct in vitro osteogenesis remains unknown. GSPCs cultured in vitro in PRF to optimally stimulate osteogenic differentiation has been largely overlooked. The aim of this study was to analyze GSPCs cultured in PRF osteogenic differentiation predicted by CBF-α1/Sox9. Methods: This study used a true experimental with post-test only control group design and random sampling. GPSCs isolated from the lower gingiva of four healthy, 250-gram, 1-month old, male Wistar rats ( Rattus Novergicus) were cultured for two weeks, passaged every 4-5 days. GSPCs in passage 3-5 were cultured in five M24 plates (N=108; n=6/group) for Day 7, Day 14, and Day 21 in three different mediums (control negative group: αModified Eagle Medium; control positive group: High Glucose-Dulbecco's Modified Eagle Medium (DMEM-HG) + osteogenic medium; Treatment group: DMEM-HG + osteogenic medium + PRF). CBF-α1 and Sox9 were examined with ICC monoclonal antibody. A one-way ANOVA continued with Tukey HSD test (p<0.05) based on Kolmogorov-Smirnov and Levene's tests (p>0.05) was performed. Results: The treatment group showed the highest CBF-α1/Sox9 ratio (16.00±3.000/14.33±2.517) on Day 7, while the lowest CBF-α1/Sox9 ratio (3.33±1.528/3.67±1.155) occurred in the control negative group on Day 21, with significant difference between the groups (p<0.05). Conclusion: GSPCs cultured in PRF had potential osteogenic differentiation ability predicted by the CBF-α1/sox9 ratio.
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Affiliation(s)
- Alexander Patera Nugraha
- Graduate School of Immunology, Postgraduate School, Universitas Airlangga, Surabaya, 60132, Indonesia
- Orthodontic Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, 60132, Indonesia
| | - Ida Bagus Narmada
- Orthodontic Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia
| | - Diah Savitri Ernawati
- Oral Medicine Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia
| | - Aristika Dinaryanti
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, 60132, Indonesia
| | - Eryk Hendrianto
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, 60132, Indonesia
| | - Igo Syaiful Ihsan
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, 60132, Indonesia
| | - Wibi Riawan
- Biochemistry Biomolecular Laboratory, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
| | - Fedik Abdul Rantam
- Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, 60132, Indonesia
- Virology and Immunology Laboratory, Microbiology Department, Faculty of Veterinary Medicine, Universitas Airlangga., Surabaya, 60132, Indonesia
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Safari S, Mahdian A, Motamedian SR. Applications of stem cells in orthodontics and dentofacial orthopedics: Current trends and future perspectives. World J Stem Cells 2018; 10:66-77. [PMID: 29988866 PMCID: PMC6033713 DOI: 10.4252/wjsc.v10.i6.66] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/19/2018] [Accepted: 05/09/2018] [Indexed: 02/06/2023] Open
Abstract
A simple overview of daily orthodontic practice involves use of brackets, wires and elastomeric modules. However, investigating the underlying effect of orthodontic forces shows various molecular and cellular changes. Also, orthodontics is in close relation with dentofacial orthopedics which involves bone regeneration. In this review current and future applications of stem cells (SCs) in orthodontics and dentofacial orthopedics have been discussed. For craniofacial anomalies, SCs have been applied to regenerate hard tissue (such as treatment of alveolar cleft) and soft tissue (such as treatment of hemifacial macrosomia). Several attempts have been done to reconstruct impaired temporomandibular joint. Also, SCs with or without bone scaffolds and growth factors have been used to regenerate bone following distraction osteogenesis of mandibular bone or maxillary expansion. Current evidence shows that SCs also have potential to be used to regenerate infrabony alveolar defects and move the teeth into regenerated areas. Future application of SCs in orthodontics could involve accelerating tooth movement, regenerating resorbed roots and expanding tooth movement limitations. However, evidence supporting these roles is weak and further studies are required to evaluate the possibility of these ideas.
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Affiliation(s)
- Shiva Safari
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran
| | - Arezoo Mahdian
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran
| | - Saeed Reza Motamedian
- Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 13819, Iran.
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Hong C, Song D, Lee DK, Lin L, Pan HC, Lee D, Deng P, Liu Z, Hadaya D, Lee HL, Mohammad A, Zhang X, Lee M, Wang CY, Ho D. Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen-nanodiamond hydrogel. Proc Natl Acad Sci U S A 2017; 114:E7218-E7225. [PMID: 28808036 PMCID: PMC5584423 DOI: 10.1073/pnas.1704027114] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17β-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.
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Affiliation(s)
- Christine Hong
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095;
| | - Dayoung Song
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Dong-Keun Lee
- Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Lawrence Lin
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Hsin Chuan Pan
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Deborah Lee
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Peng Deng
- Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Zhenqing Liu
- Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Danny Hadaya
- Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Hye-Lim Lee
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697
| | - Abdulaziz Mohammad
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Xinli Zhang
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Min Lee
- Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Cun-Yu Wang
- Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095
| | - Dean Ho
- Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, CA 90095
- Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095
- Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095
- California NanoSystems Institute, University of California, Los Angeles, CA 90095
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Identification of Differential Genes Expression Profiles and Pathways of Bone Marrow Mesenchymal Stem Cells of Adolescent Idiopathic Scoliosis Patients by Microarray and Integrated Gene Network Analysis. Spine (Phila Pa 1976) 2016; 41:840-55. [PMID: 26679893 DOI: 10.1097/brs.0000000000001394] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Microarray approach and integrated gene network analysis. OBJECTIVE To explore the differential genetic expression profile, gene ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in bone marrow mesenchymal stem cells (BM-MSCs) of idiopathic scoliosis (AIS) and non-AIS controls. SUMMARY OF BACKGROUND DATA The pathogenesis of adolescent AIS and the accompanying generalized osteopenia remain unclear. Our previous study suggested increased proliferation ability and decreased osteogenic differentiation ability of BM-MSCs of AIS. Therefore, we hypothesized that MSCs may play a significant role in the etiology and pathogenesis of AIS. METHODS In this study, microarray analysis was used to identify differentially expressed genes (DEGs) of BM-MSCs from AIS patients compared with those from healthy individuals. Comprehensive bioinformatics analyses were then used to enrich datasets for gene ontology and pathway. Based on the gene signal transduction network analysis of DEGs contained in significant pathways, 24 potential crucial genes were selected for validation by reverse transcription polymerase chain reaction. RESULTS There are 1027 previously unrecognized DEGs in BM-MSCs from AIS patients. Pathway analysis revealed dysregulated mitogen-activated protein kinase (MAPK) signaling pathway, PI3K-Akt signaling pathway, calcium signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, ubiquitin-mediated proteolysis, and Notch signaling pathway, all of which have been reported to play an important role in regulating the osteogenic or adipogenic differentiation of MSCs. Furthermore, gene signal transduction networks analysis indicated that mitogen-activated protein kinase kinase 1 (MAP2K1), SMAD family member 3 (SMAD3), homeobox C6 (HOXC6), heat shock 70kDa protein 6 (HSPA6), general transcription factor IIi (GTF2I), CREB binding protein (CREBBP), phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2), and dual specificity phosphatase 2 (DUSP2) may play essential roles in AIS pathogenesis and accompanied osteopenia. CONCLUSION This study reports the differential genes expression profiles of BM-MSCs from AIS patients and related potential pathways for the first time. These previously unrecognized genes and molecular pathways might play a significant role in not only the causal mechanism of osteopenia in AIS, but also the AIS initiation and development. The identification of these candidate genes provides novel insight into the underlying etiological mechanisms of AIS. LEVEL OF EVIDENCE N/A.
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Buyuk SK, Ramoglu SI, Sonmez MF. The effect of different concentrations of topical ozone administration on bone formation in orthopedically expanded suture in rats. Eur J Orthod 2015; 38:281-5. [PMID: 26136437 DOI: 10.1093/ejo/cjv045] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/OBJECTIVE The aim of this study was to investigate the effects of different concentrations of ozone (O3) therapy on bone regeneration in response to an expansion of the inter-premaxillary suture in rats. MATERIALS AND METHODS Forty-eight Wistar rats were randomly divided into four groups (n = 12). In groups I, II, and III, 1ml of O3 at 10, 25, and 40 µg/ml was injected at the premaxillary suture, respectively. In group IV (control group), 1ml of saline solution was injected at the same point during the expansion procedure for 5 days. Bone regeneration in the suture was evaluated histomorphometrically. The area of new bone and fibrotic area, the number of osteoblasts and osteoclasts, and the amount of vascularity were measured and compared. The density of the newly formed bone in the expansion area was measured by using cone beam computed tomography. Data were analyzed using the Kruskal-Wallis one-way analysis of variance and post hoc Student-Newman-Keuls tests. RESULTS New bone area, fibrotic area, osteoblast and osteoclast numbers, and the amount of vascularity were significantly higher in experimental groups compared with the control group (P < 0.001). The density of newly formed bone (P < 0.001), new bone formation (P = 0.009), number of capillaries (P < 0.001), number of osteoclasts (P = 0.016), and number of osteoblasts (P < 0.001) in the maxillary sutures were highest in the 25 μg/ml O3 group compared with the other experimental groups and control group. CONCLUSIONS/IMPLICATIONS The application of O3 therapy can stimulate bone regeneration in an orthopedically expanded inter-premaxillary suture during both the expansion and retention periods.
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Affiliation(s)
- S Kutalmış Buyuk
- *Department of Orthodontics, Faculty of Dentistry, Ordu University, Ordu, Turkey,
| | - Sabri Ilhan Ramoglu
- **Department of Orthodontics, Faculty of Dentistry, Bezmialem Vakıf University, Istanbul, Turkey and
| | - Mehmet Fatih Sonmez
- ***Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
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Kaneko K, Matsuda S, Muraoka R, Nakano K, Iwasaki T, Tomida M, Tsujigiwa H, Nagatsuka H, Kawakami T. Histological Evaluation of Periodontal Ligament in Response to Orthodontic Mechanical Stress in Mice. Int J Med Sci 2015; 12:689-94. [PMID: 26392805 PMCID: PMC4571545 DOI: 10.7150/ijms.12883] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 07/26/2015] [Indexed: 12/04/2022] Open
Abstract
The purpose of the study was to determine the cell dynamics in periodontal ligament in response to mechanical stress during orthodontic movement. Following Waldo's method, a square sheet of rubber dam was inserted in between the first and second maxillary molars in 10 ddY mice leaving the stress load for 3 hours. After 3 days and at 1 week, cell count on pressure and tension sides of the periodontal ligament was determined. Furthermore, the type of cell present after mechanical stress was identified using GFP bone marrow transplantation mouse model. Immunohistochemistry was carried out at 0 min (immediately after mechanical stress), 24 hours, 1 week, 2 weeks and 6 months. Temporal changes in the expression of GFP-positive bone marrow derived cells were examined. Moreover, double immunofluorescent staining was performed to determine the type of cell in the periodontal ligament. Cell count on the tension side tremendously increased 3 days after mechanical stress. At 1 week, spindle and round cell count increased compared to the control group. These changes were observed on both tension and pressure sides. Cell count on pressure side at 3 days (22.11+/-13.98) and at 1 week (33.23+/-11.39) was higher compared to the control group (15.26+/-8.29). On the tension side, there was a significantly increased at 3 days (35.46+/-11.85), but decreased at 1 week (29.23+/-13.89) although it is still higher compared to the control group (AD+/-SD: 10.37+/-8.69). Using GFP bone marrow transplantation mouse model, GFP positive cell count increased gradually over time in 6 months. GFP positive cells were also positive to CD31, CD68 and Runx2 suggesting that fibroblasts differentiated into osteoclasts and tissue macrophages. In conclusion, mechanical stress during orthodontic movement promoted the increase in the number of cells in the periodontal ligament on both tension and pressure sides. The increase in the number of cells in the periodontal ligament is believed to be due to the migration and cell division of undifferentiated mesenchymal cells.
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Affiliation(s)
- Keiko Kaneko
- 1. Department of Hard Tissue Research, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri, Japan
| | - Saeka Matsuda
- 1. Department of Hard Tissue Research, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri, Japan
| | - Rina Muraoka
- 2. Department of Orthodontics, Matsumoto Dental University School of Dentistry, Shiojiri, Japan
| | - Keisuke Nakano
- 1. Department of Hard Tissue Research, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri, Japan ; 3. Department of Oral Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Takami Iwasaki
- 4. Department of Social Dentistry, Matsumoto Dental University School of Dentistry, Shiojiri, Japan
| | - Mihoko Tomida
- 4. Department of Social Dentistry, Matsumoto Dental University School of Dentistry, Shiojiri, Japan
| | - Hidetsugu Tsujigiwa
- 5. Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan
| | - Hitoshi Nagatsuka
- 3. Department of Oral Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Toshiyuki Kawakami
- 1. Department of Hard Tissue Research, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri, Japan
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