Osteoarthritis is thought to be a NLRP3-related disease. NEK7 is an essential mediator for NLRP3
inflammasome activation. This study aimed to demonstrate whether NEK7 has regulatory roles in the pathogenesis of
osteoarthritis. C57BL/6 mice were subjected to anterior cruciate ligament transection
osteoarthritis (ACLT) for constructing animal models of
osteoarthritis. Injection of adeno-associated virus (AAV) expressing NEK7-specific
shRNA into the knee joints of mice, following of which immunohistochemistry, qRT-PCR, western blotting,
Safranin-O Fast Green staining, ELISA, and co-immunoprecipitation were performed to determine the effects of NEK7. NEK7 was highly expressed in the joint tissues of ACLT mice. As compared with shScr, AAV delivery of NEK7
shRNA significantly inhibited cartilage degeneration, OARSI score, and serum CTX-II and COMP levels. AAV delivery of NEK7
shRNA downregulated the expression of matrix-degrading
enzymes (ADAMTS-4, MMP3, and MMP13) and upregulated the expression of ECM-related molecules (SOX9,
collagen II, and
aggrecan). In addition, AAV delivery of NEK7
shRNA alleviated ACLT-induced synovial
inflammation, as was evidenced by the decreased levels of TNF-α,
IL-6, IL-1β, and
IL-18 and increased levels of
IL-10. In the joint tissues of ACLT mice, NEK7 interacted with NLRP3
proteins. AAV delivery of NEK7
shRNA inhibited the
protein interaction, and thereby inhibited the activation of the NLRP3
inflammasome. AAV delivery of NEK7
shRNA has no significant effects on cartilage degeneration and synovial
inflammation in Nlrp3-/- mice. In conclusion, knockdown of NEK7 exerted anti-osteoarthritic effects, possibly via inhibiting the activation of the NLRP3
inflammasome. This study provided a novel mechanism of NEK7-NLRP3 interaction affecting
osteoarthritis.