Journal of Cellular and Molecular Medicine · Apr 2025

FKBP5 Induces Senescence in BMSCs and Inhibits Osteogenic Differentiation Through the Canonical WNT/β-Catenin Signalling Pathway in Senile Osteoporosis

By Zhu B, Cai B, Xue K et al.

Senile osteoporosis and its associated fractures significantly contribute to increased morbidity, mortality, and healthcare costs among older adults. Further research is needed to elucidate the molecular mechanisms underlying senile osteoporosis. This study found that FKBP5 expression in bone marrow mesenchymal stem cells (BMSCs) increases with age and is inversely correlated with patients' bone mineral density and CT values. Functional analyses revealed that FKBP5 plays a crucial regulatory role in BMSC osteogenic differentiation, acting through the canonical WNT/β-catenin signalling pathway. FKBP5 binds to β-catenin, promoting its ubiquitination and degradation. Importantly, administration of SAFit2, a selective FKBP5 inhibitor, enhanced bone mineral density in an animal model of senile osteoporosis. These findings suggest that FKBP5 may represent a novel therapeutic target and provide new insights into the treatment of senile osteoporosis.

doi.org/10.1111/jcmm.70552 Open access PubMed 40254776 Mechanisms