Mechanical overloading leads to chondrocyte degeneration and senescence via Zmpste24-mediated nuclear membrane instability.

ABSTRACT: Patients with OA and varus knees are subject to abnormal mechanical environment and objective of this study was to investigate the molecular mechanisms underlying chondrocyte senescence caused by mechanical overloading and the role of Zmpste24-mediated nuclear membrane instability in varus knees. Finite element analysis showed that anteromedial region of tibial plateau experienced the most mechanical stress in an osteoarthritis patient with a varus knee. Immunohistochemistry exhibited lower Zmpste24 expression and higher expression of senescence marker p21 in the anteromedial region. Animal experiments and cell-stretch models also demonstrated an inverse relationship between Zmpste24 and mechanically induced senescence. Zmpste24 overexpression rescued cartilage degeneration and senescence

SUBMITTER: Kong K 

PROVIDER: S-EPMC10641493 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature