CD137 Regulates Bone Loss via the p53 Wnt/b-Catenin Signaling Pathways in Aged Mice

Senile osteoporosis is a chronic skeletal disease that increases bone fragility and fracture risk, becoming a significant global health concern with an aging population. The molecular mechanism of how osteoporosis is caused is still not clear. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. The study used bioinformatics analysis of gene expression profiles to identify CD137 as a promising gene involved in osteoporosis. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/b-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Experiments on aged mice showed significant bone loss and increased bone marrow fat compared to young mice. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis.

• 1
  Aged mice (18-month-old) exhibited significant bone loss compared to young mice (6-month-old), along with a tenfold increase in adipose tissue in the bone marrow cavity.
• 2
  Bioinformatics analysis and in vivo experiments suggest that CD137 is involved in the p53 and canonical Wnt/β-catenin signaling pathways, influencing bone mass by regulating marrow adipogenesis.
• 3
  Blocking CD137 signaling in vivo rescued osteoporosis in aged mice, indicating its importance in the regulation of adipogenic capacity in senile osteoporosis.