Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis.

ABSTRACT: Recent evidence suggests an association between age-related osteoporosis and cellular senescence in the bone; however, the specific bone cells that play a critical role in age-related osteoporosis and the mechanism remain unknown. Results revealed that age-related osteoporosis is characterized by the loss of osteoblast Men1. Osteoblast-specific inducible knockout of Men1 caused structural changes in the mice bones, matching the phenotypes in patients with age-related osteoporosis. Histomorphometrically, Men1-knockout mice femurs decreased osteoblastic activity and increased osteoclastic activity, hallmarks of age-related osteoporosis. Loss of Men1 induces cellular senescence via mTORC1 activation and AMPK suppression, rescued by metformin treatment. In bone morphogenetic protein-indued bon

SUBMITTER: Ukon Y 

PROVIDER: S-EPMC11464108 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature