Departmental Papers (Dental)
Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents
Date of this Version
Article number e2615
Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studied revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)-induced osteoporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts. © 2008 Yamaza et al.
MeSH: Animals, Apoptosis, Aspirin, Bone Marrow Cells, Bone Resorption, CD4-Positive T-Lymphocytes, Humans, Interleukin-2 Receptor alpha Subunit, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Mice, Inbred C3H, Mice, Transgenic, Osteoclasts, Osteoporosis, T-Lymphocytes Species Index: Mus, Rodentia EMTREE drug terms: acetylsalicylic acid, Fas antigen, Fas ligand, telomerase, acetylsalicylic acid, interleukin 2 receptor alpha EMTREE medical terms: adult, animal cell, animal experiment, animal model, apoptosis, article, bone density, bone development, controlled study, drug mechanism, enzyme activity, enzyme inhibition, ex vivo study, female, human, human cell, in vitro study, mesenchymal stem cell, mouse, nonhuman, ossification, osteoblast, osteoclast, osteolysis, osteoporosis, ovariectomy, T lymphocyte, T lymphocyte activation, animal, bone marrow cell, C3H mouse, CD4+ T lymphocyte, drug effect, immunology, mesenchymal stem cell, mesenchymal stem cell transplantation, metabolism, transgenic mouse
Yamaza, T., Miura, Y., Bi, Y., Liu, Y., Akiyama, K., Sonoyama, W., Patel, V., Gutkind, S. J., Young, M. F., Gronthos, S., Le, A., Wang, C., Chen, W., & Shi, S. (2008). Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents. PLoS ONE, 3 (7), Article number e2615-. http://dx.doi.org/10.1371/journal.pone.0002615
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Anh D. Le was affiliated with the Center for Craniofacial Molecular Biology, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Songtao Shi was affiliated with the Center for Craniofacial Molecular Biology, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.