β1,4-galactosyltransferase-I protects chondrocytes against TNF-induced apoptosis by blocking the TLR4 signaling pathway.

Osteoarthritis (OA) is the most common degenerative disease of the cartilage and is characterized by inflammation of the synovial membrane and subchondral osteosclerosis. β1,4-galactosyltransferase-I (β1,4-GalT-I) is a crucial regulator of inflammation based on its role in the stimulation and sustenance of inflammation in OA. In the present study, we aimed at elucidating the expression pattern and potential biological activity of β1,4-GalT-I in chondrocytes isolated from OA patients. Chondrocytes were isolated from the cartilage and cultured. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to analyze β1,4-GalT-I expression. Isolated chondrocytes were stimulated with tumor necrosis factor (TNF). Our results indicate significantly enhanced expression of β1,4-GalT-I in cultivated chondrocytes upon stimulation with TNF. β1,4-GalT-I inhibited the inflammation and cell death triggered by TNF. In addition, β1,4-GalT-Iinhibited the expression of Toll-like receptor 4 (TLR4) and phosphorylation of p65 and IKK. In conclusion, our findings suggest the protective effect of β1,4-GalT-I in chondrocytes against OA induced by TNF based on its ability to block the TLR4 signaling pathway. Our results also indicate significant contribution of β1,4-GalT-I towards the anti-inflammation in the cartilage of patients suffering from OA.