Mitochondrial dysfunction in mesenchymal stem cells impairs osteogenesis in radiation-induced bone injury via Ca²⁺-NFATc1-Fis1 pathway.

ABSTRACT: Mitochondrial dysfunction of mesenchymal stem cells (MSCs) has been implicated in impaired osteogenesis, resulting in bone loss following radiation therapy. However, the underlying mechanisms remain to be fully elucidated. This study reveals the critical role of Fis1 in regulating mitochondrial dynamics and MSC osteogenesis in radiation-induced bone injury. Specifically, radiation activates Fis1 expression, which induces excessive mitochondrial fission, leading to mitochondrial fragmentation, along with reduced capacities for oxidative phosphorylation, ATP synthesis, and antioxidant defense, that collectively impairs MSC osteogenesis and results in bone loss in radiation-induced bone injury. This process involves increased calcium (Ca²⁺) influx that stimulates calcineurin (CaN)

SUBMITTER: Ren L 

PROVIDER: S-EPMC12828000 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature