CZFP609 Tethering BiP Alleviates Cartilage Degradation in Osteoarthritis via Remedying Aberrant ER-Mitochondrial Contacts.

ABSTRACT: Vascular dysfunction is implicated in the pathogenesis of osteoarthritis (OA). Herein, we utilized smooth muscle specific human Sirt1 transgenic (smSirt1-Tg) mice characterized by vascular homeostasis to prepare an OA model to validate vasculature-derived articular cartilage protective factors. The OA of smSirt1-Tg mice exhibited significantly reduced cartilage destruction and pain sensitivity, accompanied by increased proteoglycans content and collagen type II (Col2ɑ) expression and decreased matrix metallopeptidase 13 (MMP13) and p53 expression. Vascular smooth muscle cell-derived cZFP609 was highly enriched in the articular cartilage and plasma of smSirt1-Tg mice. Overexpression of cZFP609 abrogated TNFα-induced endoplasmic reticulum (ER) stress and fine-tune

SUBMITTER: Song Y 

PROVIDER: S-EPMC12516089 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature