MiR-155 promotes interleukin-1β-induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1-mediated PI3K/Akt pathway.

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA-155 (miR-155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR-155 is associated with OA pathology remain unexplored. We report here that miR-155 level is significantly up-regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin-1β (IL-1β), a pivotal pro-catabolic factor promoting cartilage degradation. Moreover, miR-155 inhibition attenuates and its overexpression promotes IL-1β-induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3-kinase (PI3K)) is a target of miR-155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR-155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR-155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR-155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1-mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR-155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression.