Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents

Takayoshi Yamaza, Yasuo Miura, Yanming Bi, Yongzhong Liu, Kentaro Akiyama, Wataru Sonoyama, Voymesh Patel, Silvio Gutkind, Marian Young, Stan Gronthos, Anh Le, Cun Yu Wang, Wan Jun Chen, Songtao Shi

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numbere2615
JournalPloS one
Volume3
Issue number7
DOIs
Publication statusPublished - Jul 9 2008
Externally publishedYes

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osteoporosis
Stem cells
Osteoporosis
stem cells
Rodentia
Bone
rodents
Stem Cells
aspirin
Aspirin
bone marrow cells
Mesenchymal Stromal Cells
osteoclasts
Fas Ligand Protein
bone density
T-cells
Osteoclasts
apoptosis
T-lymphocytes
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. / Yamaza, Takayoshi; Miura, Yasuo; Bi, Yanming; Liu, Yongzhong; Akiyama, Kentaro; Sonoyama, Wataru; Patel, Voymesh; Gutkind, Silvio; Young, Marian; Gronthos, Stan; Le, Anh; Wang, Cun Yu; Chen, Wan Jun; Shi, Songtao.

In: PloS one, Vol. 3, No. 7, e2615, 09.07.2008.

Research output: Contribution to journalArticle

Yamaza, T, Miura, Y, Bi, Y, Liu, Y, Akiyama, K, Sonoyama, W, Patel, V, Gutkind, S, Young, M, Gronthos, S, Le, A, Wang, CY, Chen, WJ & Shi, S 2008, 'Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents', PloS one, vol. 3, no. 7, e2615. https://doi.org/10.1371/journal.pone.0002615
Yamaza, Takayoshi ; Miura, Yasuo ; Bi, Yanming ; Liu, Yongzhong ; Akiyama, Kentaro ; Sonoyama, Wataru ; Patel, Voymesh ; Gutkind, Silvio ; Young, Marian ; Gronthos, Stan ; Le, Anh ; Wang, Cun Yu ; Chen, Wan Jun ; Shi, Songtao. / Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. In: PloS one. 2008 ; Vol. 3, No. 7.
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AU - Sonoyama, Wataru

AU - Patel, Voymesh

AU - Gutkind, Silvio

AU - Young, Marian

AU - Gronthos, Stan

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AU - Chen, Wan Jun

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N2 - 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.

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