Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! By
Restoring Impaired Osteogenic Differentiation of Diabetic Rat Stromal Cells Using Epigenetic Inhibitors Publisher Pubmed



M Hodjat MAHSHID ; F Khan FAZLULLAH ; H Mohammadpour HADISEH ; N Asadi NASRIN
Authors

Source: Advances in Medical Sciences Published:2025


Abstract

Purpose: Epigenetic regulation plays a crucial role in gene expression and is recognized as a key contributor to diabetes-related complications. This study explores the osteogenic differentiation potential of stem cells isolated from the periodontal ligament (PDL) and bone marrow (BM) of diabetic rats. It investigates the effects of DNA methyltransferase and histone deacetylase inhibitors on the differentiation capacity of diabetic stem cells, searching for underlying mechanisms. Method: Diabetes was induced in 5-week-old male Wistar rats using streptozotocin (STZ). Bone parameters were assessed via micro-CT, and stem cells isolated from mandibles and femurs were treated with 5-azacytidine or Trichostatin A in osteogenic medium. Osteogenic differentiation was evaluated through alkaline phosphatase (ALP) activity, Alizarin Red staining, and mRNA expression of osteogenic markers using real-time PCR. Results: A significant decrease in total BMD and BV/TV of the femur and mandible was observed in STZ-induced diabetic rats compared to control. Cells isolated from diabetic PDL and BM showed impaired mineralization capacity and downregulated osteogenic markers. Treatment with Trichostatin A or 5-azacytidine restored mineralization potential, increased ALP activity, and upregulated the expression of RUNX2 and β-catenin. Conclusion: Our results revealed the underlying epigenetic mechanisms responsible for the impaired osteogenic differentiation capacity of stem cells in diabetes. These findings highlight the potential of epigenetic modulators to restore stem cell function and enhance bone regeneration. This approach holds promise for improving diabetes-related skeletal complications and advancing tissue engineering strategies, including the development of scaffold-based therapies for fracture repair, periodontal regeneration, and implant integration in diabetic patients. © 2025 Elsevier B.V., All rights reserved.
Related Docs
View other Related Docs
1. Histone Deacetylase Inhibitors Restore the Odontogenic Differentiation Potential of Dental Pulp Stem Cells Under Hyperglycemic Conditions, Current Stem Cell Research and Therapy (2025)
2. Epigenetic Regulation of Specific Transcription Factors in Osteogenic Differentiation of Mesenchymal Stem Cells, Turkish Journal of Biology (2016)
3. Epigenetic Changes Underlie the Association Between Diabetes Mellitus and Oral Diseases, Molecular Biology Reports (2023)
Experts (# of related papers)
View all Related Experts
Mahshid Hodjat (3)
Fatemeh Mohammadian Rasnani (1)
Other Related Docs
4. In Vitro Proliferation and Osteogenic Differentiation of Endometrial Stem Cells and Dental Pulp Stem Cells, Cell and Tissue Banking (2017)
5. Acceleration of a Delayed Healing Wound Repair Model in Diabetic Rats by Additive Impacts of Photobiomodulation Plus Conditioned Medium of Adipose-Derived Stem Cells, Journal of Diabetes and Metabolic Disorders (2023)
6. Mechanisms Involved in Altered Bone Metabolism in Diabetes: A Narrative Review, Journal of Diabetes and Metabolic Disorders (2016)
7. Adipose-Derived Stem Cells-Conditioned Medium Improved Osteogenic Differentiation of Induced Pluripotent Stem Cells When Grown on Polycaprolactone Nanofibers, Journal of Cellular Physiology (2019)
8. Different Protocols of Combined Application of Photobiomodulation in Vitro and in Vivo Plus Adipose-Derived Stem Cells Improve the Healing of Bones in Critical Size Defects in Rat Models, Journal of Lasers in Medical Sciences (2022)
9. Diabetes Mellitus and Osteoporosis Correlation: Challenges and Hopes, Current Diabetes Reviews (2020)
10. Evaluation of the Effect of Adipose Tissue-Derived Stem Cells on the Quality of Bone Healing Around Implants, Connective Tissue Research (2016)
11. The Association Between Bone Turnover Markers and Microvascular Complications of Type 2 Diabetes, Journal of Diabetes and Metabolic Disorders (2016)
12. The Generation of Islet-Like Insulin-Producing Cells From Wharton's Jelly-Derived Mesenchymal Stem Cells on the Pes/Fish Gelatin Scaffold, Regenerative Therapy (2024)
13. Diabetic Wound Healing Via a Co-Delivery System for Bone Marrow Derived Stem Cells and Euphorbia Hirta Extract: An in Vitro and in Vivo Study, Journal of Materials Science: Materials in Medicine (2025)
14. Osteogenic Differentiation of Human Induced Pluripotent Stem Cell in the Presence of Testosterone and 17 Β-Estradiol in Vitro, In Vitro Cellular and Developmental Biology - Animal (2022)
15. The Effects of Umbilical Cord Wharton Jelly Derived Mesenchymal Stem Cells Injection on Diabetic Wound Healing in Male Rats, Tehran University Medical Journal (2021)
16. Preconditioning Adipose-Derived Stem Cells With Photobiomodulation Significantly Increased Bone Healing in a Critical Size Femoral Defect in Rats, Biochemical and Biophysical Research Communications (2020)
17. Adipose Tissue-Derived Mesenchymal Stem Cells Exert in Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model, Journal of Diabetes Research (2015)
18. Effect of Photobiomodulation Therapy With 660 and 980 Nm Diode Lasers on Differentiation of Periodontal Ligament Mesenchymal Stem Cells, Scientific Reports (2024)
19. Study the Effect of Low-Level Laser Therapy on Osteogenic Capacity of Periodontal Ligament Stem Cell: An in Vitro Study, Journal of Laser Applications (2025)
20. Combined Therapy of Adipose-Derived Stem Cells and Photobiomodulation on Accelerated Bone Healing of a Critical Size Defect in an Osteoporotic Rat Model, Biochemical and Biophysical Research Communications (2020)