The relationship between abnormal Core binding factor-β expression in human cartilage and osteoarthritis

Abstract

Abstract Background This study aimed to investigate the effect of abnormal Core binding factor-β expression on proliferation, differentiation and apoptosis of chondrocytes, and elucidate the relationship between Core binding factor-β and osteoarthritis-related markers and degenerative joint disease. Methods Cartilage tissues, from healthy subjects and patients with osteoarthritis, were collected for histology and expression of Core binding factor-β, MMP-13, IL-1β, COMP, and YKL-40. Human articular chondrocytes were cultured in vitro, and a viral vector was constructed to regulate cellular Core binding factor-β expression. Cellular proliferation and apoptosis were observed, and osteoarthritis-related inflammatory factor expression and cartilage metabolite synthesis assayed. Results Human osteoarthritis lesions had disordered cartilage structure and cellular arrangement, and increased emptying of cartilage lacunae. Normal cell counts were significantly reduced, cartilage extracellular matrix was obviously damaged, and type II collagen expression was significantly decreased. Core binding factor-β was highly expressed in the osteoarthritis cartilage (p < 0.001), and MMP-13, IL-1β, COMP and YKL-40 expression were greater than found in normal cartilage (p < 0.001). Cellular proliferation in the Core binding factor-β high-expression group was reduced and the total apoptosis rate was increased (p < 0.05), while the opposite was found in the Core binding factor-β inhibition group (p < 0.01). Compared with normal chondrocytes, high Core binding factor-β expression (Osteoarthritis and CBFB/pCDH groups) was associated with significantly increased MMP13, IL-1β, COMP and YKL-40 protein expression (p < 0.01), while Core binding factor-β inhibition (CBFB/pLKO.1 group) was associated with significantly decreased COMP, MMP13, IL-1β and YKL-40 expression in osteoarthritis cells (p < 0.001). Conclusions Abnormal Core binding factor-β expression might play an upstream regulatory role in mediating abnormal chondrocyte apoptosis and the inflammatory response. On inhibiting Core binding factor-β expression, a delay in cartilage degeneration was expected. Trial registration The study was registered for clinical trials in ChiCTR: ChiCTR1800017066 (Reg. Date-2018/7/10).

Keywords

• Core binding factor-β
• Osteoarthritis
• MMP-13
• IL-1beta
• COMP