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

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).

Cbfβ regulates Wnt/β-catenin, Hippo/Yap, and Tgfβ signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis

“…These epigenetic changes could be the result of internal factors such as genetics or external factors such as diet, exercise, and environmental exposures. Interestingly, Li et al reported the relationship between abnormal CBFB expression in human cartilage and OA and reported that CBFB was highly expressed in the osteoarthritic cartilage ( Li et al, 2021 ). However, in our study and Che et al’s report ( Che et al, 2023 ), CBFB expression in human OA was decreased compared to human normal cartilage.…”

Deficiency of Cbfβ in articular cartilage leads to osteoarthritis-like phenotype through Hippo/Yap, TGFβ, and Wnt/β-catenin signaling pathways

“…During postnatal skeletal development, Cbfβ mediated chondrocyte maturation is pivotal for trabecular bone morphogenesis 13 . Further, Guofeng Li et al and Guangdi Li et al found that Cbfβ is the one of potential key transcriptional factors in human cartilage and OA 19 , 20 , and the protein expression of Cbfβ in cartilages of human OA decreased significantly 21 . These studies suggest that Cbfβ may play an important role in OA, nevertheless, the function of Cbfβ in OA pathogenesis is still lacking the validation of loss-of-function animal model.…”

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

“…Although chondrocytes are in the active proliferation stage, the main content of ECM, glycosaminoglycans, are significantly lower, indicating that the chondrocytes compensation level remains lower, and the cartilage may always be in the process of degeneration 9 . While in the late stage, cartilage degeneration manifested by an increased chondrocyte death, including decreased cell density and emptying of lacunae 10 . In addition, reduction of cartilage cell vitality can also cause degeneration of articular cartilage 11 .…”

“…9 While in the late stage, cartilage degeneration manifested by an increased chondrocyte death, including decreased cell density and emptying of lacunae. 10 In addition, reduction of cartilage cell vitality can also cause degeneration of articular cartilage. 11 Thus, a proper chondrocyte density is crucial for maintaining the cartilage matrix.…”