Baicalein ameliorates inflammatory-related apoptotic and catabolic phenotypes in human chondrocytes.

Abstract

Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. In OA, pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α can trigger the caspase cascade to promote apoptosis and activate NF-κB to induce catabolic factors in chondrocytes. Here, the anti-apoptotic and anti-catabolic effects of baicalein on human OA chondrocytes treated by a mixture of IL-1β and TNF-α (IT) were investigated in vitro. In cultured chondrocytes, baicalein pretreatment attenuated apoptosis in a concentration-dependent manner in response to IT stimulation. Mechanistically, the anti-apoptotic effects of baicalein result from inhibition of nitric oxide production and downstream caspase signaling pathway. Moreover, administration of baicalein significantly reduced matrix metalloproteinase (MMP) 3 and MMP13 secretion in chondrocytes stimulated with IT. The anti-catabolic effects of baicalein were further demonstrated by the recovery of the glycosaminoglycan and type II collagen (COLII) deposition by histological analysis in IT-treated mouse articular cartilage explants. These findings suggest that baicalein might be a promising novel therapeutic agent for OA by virtue of its suppression of apoptosis and MMP secretion in OA chondrocytes.