FKBP5 drives bone marrow stem cells senescence and suppresses osteogenic differentiation via canonical WNT/β-catenin signaling pathway

Senile osteoporosis and associated fractures significantly increase the morbidity and mortality of older people, thus increasing the cost of public health. Further investigations are required to explore the molecular causes of senile osteoporosis. In this study, FKBP5 expression in bone marrow mesenchymal stem cells (BMSCs) increased with age, and the degree of expression was inversely related to the patient's bone mineral density or CT values. Functional studies have validated the regulatory function of FKBP5 in BMSCs osteogenesis differentiation through the canonical WNT/β-catenin signaling pathway by binding to β-catenin and promoting its ubiquitination and degradation. Administration of SAFit2, a selective inhibitor of FKBP5, enhanced bone density in an animal model of senile osteoporosis. These findings suggest that FKBP5 may be a novel target and offer a new perspective on osteoporosis treatment.