Galectin‐3 deficiency protects lipopolysaccharide‐induced chondrocytes injury via regulation of TLR4 and PPAR‐γ‐mediated NF‐κB signaling pathway

The aim of the present study was to identify the functional role of galectin‐3 (Gal‐3) in lipopolysaccharide (LPS)‐induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal‐3 in ATDC5 cells. In addition, repression of Gal‐3 obviously impeded LPS‐stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)‐13 and MMP‐3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal‐3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl‐2 and a decrease in the expression of proapoptotic protein Bax and caspase‐3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR‐γ with the antagonist GW9662 effectively abolished Gal‐3 inhibition–mediated anti‐inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal‐3 prevents the NF‐κB signaling pathway. Taken together, these findings indicated that the absence of Gal‐3 exerted chondroprotective properties dependent on TLR4 and PPAR‐γ‐mediated NF‐κB signaling, indicating that Gal‐3 functions as a protector in the development and progression of osteoarthritis. Absence of Gal‐3 exerted chondroprotective properties following dependent on TLR4 and PPAR‐γ‐mediated NF‐κB signaling, indicating that Gal‐3 function as a protector in the development and progression of osteoarthritis.