Background/Purpose: Osteoporosis led to severe bone-related diseases and increased mortality and health care costs. Existing treatments failed to reduce the risk of fractures in patients, so it is urgent to search new therapeutic methods for regulating bone resorption and formation.

Methods: 2×10^6 GMSC were intravenously injected to the ovariectomy (OVX) mice, trabecular bone parameters, dynamic bone formation and the frequency of osteoclasts were assessed. GMSC were pretreated with CD39 inhibitor, CD73 inhibitor or adenosine receptors to evaluate osteogenesis function in vitro and in vivo.

Results: OVX was performed in adult C57BL/6J mice after complete skeletal remodeling, and GMSC therapy was given 2 weeks after OVX. After 8 weeks of treatment, the distal femoral trabecular bone was sparse and discontinuous in OVX group, and GMSC treatment showed a clear therapeutic effect on bone density, trabecular BV/TV, trabecular numbers. GMSC treatment also resulted in a dramatically decreased frequency of osteoclasts and increased dynamic bone formation in vivo. To identify the mechanism, we found CD39 inhibitors (POM-1) inhibited the osteogenic potential of GMSC in vitro. Interestingly, POM-1 almost completely abolished the therapeutic effect of GMSC on osteoporosis. At the molecular level, we further observed that CD39 of GMSC exert their osteogenic capacity through Wnt / β-catenin pathway.

Conclusion: GMSC regulate the balance of osteoclasts and osteoblasts in osteoporosis by CD39 depending Wnt / β-catenin pathway. Our data suggests that application of GMSC represents a potential therapeutic approach for patients with osteoporosis, and highlight the key role of CD39 in the GMSC function.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cd39-produced-from-human-gingiva-derived-mesenchymal-stem-cells-regulates-the-balance-of-osteoclasts-and-osteoblasts-through-wnt-%ce%b2-catenin-pathway-in-osteoporosis/