GAB2 inhibits chondrocyte apoptosis through PI3K-AKT signaling in osteoarthritis.

Cartilage degeneration is considered the main pathologic feature of osteoarthritis (OA). Cumulative evidence indicates that chondrocyte apoptosis is associated with cartilage degradation. However, the underlying molecular mechanism of chondrocyte apoptosis remains unclear. Growth factor receptor-bound protein 2 (GAB2), an adaptor protein, belongs to the Gab family and is involved in various biologic processes. Here, we explored the role of GAB2 in the pathogenesis of osteoarthritis (OA). GAB2 expression was markedly increased in OA articular cartilage. GAB2 expression was also increased in an in vitro model of TNFα-induced apoptosis. GAB2 depletion by siRNA promoted expression of the apoptosis markers, PARP and caspase-3, and increased the number of apoptotic cells, indicating that GAB2 might have an anti-apoptotic effect in chondrocytes. Moreover, GAB2 knockdown inhibited AKT phosphorylation, increased BAX expression, and decreased BCL2 expression, which indicated that GAB2 regulates chondrocyte apoptosis through PI3K-AKT signaling. Taken together, our study indicates that GAB2 plays a vital role in chondrocyte apoptosis and provides a new therapeutic target for OA.