LAUSR

C1q/tumor necrosis factor‐related protein 9 (CTRP9) has been identified as a novel anti‐inflammatory factor that participates in numerous pathological conditions. However, whether CTRP9 participates in the regulation of osteoarthritis has not been studied. This work sought to determine the possible role of CTRP9 in osteoarthritis using an in vitro model, namely interleukin‐1β (IL‐1β)‐stimulated chondrocytes. There was a decreased level of CTRP9 in chondrocytes after IL‐1β stimulation. CTRP9 upregulation dramatically repressed IL‐1β‐evoked apoptosis and inflammatory response in cultured chondrocytes. The mechanistic investigation revealed that CTRP9 overexpression restrained the activation of the nucleotide‐binding oligomerization domain‐like receptor 3 (NLRP3) inflammasome in IL‐1β‐stimulated chondrocytes via the adiponectin receptor 1 (AdipoR1)/adenosine monophosphate‐activated protein kinase (AMPK) axis. Notably, inhibition of AdipoR1 or AMPK abolished the regulatory effects of CTRP9 overexpression on IL‐1β‐evoked apoptosis and inflammasome activation. Overall, the results of this work delineate that CTRP9 protects cultured chondrocytes from IL‐1β‐induced inflammatory injury by inhibiting NLRP3 inflammasome activation via the AdipoR1/AMPK axis. This work underscores a potential role of CTRP9 in the progression of osteoarthritis.