Cbf beta Is a Novel Modulator against Osteoarthritis by Maintaining Articular Cartilage Homeostasis through TGF-beta Signaling

卷:12

Article

关键词: BINDING-FACTOR BETA;    TRANSCRIPTION FACTOR;    CHONDROCYTE MATURATION;    OSTEOPHYTE FORMATION;    BONE-FORMATION;    DIFFERENTIATION;    EXPRESSION;    RECEPTOR;    RUNX2;    INDUCTION;   

DOI  :  10.3390/cells12071064

来源: SCIE

【 摘 要 】

TGF-beta signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-beta signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor beta (Cbf beta) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbf beta in maintaining articular cartilage integrity remains obscure. This study investigated Cbf beta as a novel anabolic modulator of TGF-beta signaling and determined its role in articular cartilage homeostasis. Cbf beta significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb4ac/ 4ac) exhibited early cartilage degeneration at 20 weeks of age and developed OA at 12 months. Cbfb4ac/ 4ac mice showed enhanced OA progression under the surgically induced OA model in mice. Mechanistically, forced expression of Cbf beta rescued Type II collagen (Col2 alpha 1) and Runx1 expression in Cbf beta-deficient chondrocytes. TGF-beta 1-mediated Col2ff1 expression failed despite the p-Smad3 activation under TGF-beta 1 treatment in Cbf beta-deficient chondrocytes. Cbf beta protected Runx1 from proteasomal degradation through Cbf beta/Runx1 complex formation. These results indicate that Cbf beta is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbf beta could protect OA development by maintaining the integrity of the TGF-beta signaling pathway in articular cartilage.