WITHDRAWN: Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP-RIPK1-NF-κB axis via influencing autophagy

Abstract

Osteoarthritis (OA), known as a degenerative disease which characterized by the chronic inflammation of the joint. Unfortunately, due to the limited understanding of its pathological mechanism, there are no effective drugs or treatments to suspend the progression of OA. Interestingly, LIPUS had been reported to have a positive effect on many diseases including OA, but the exact mechanism of how LIPUS plays a role in OA remains unknown. In this study, we demonstrated that P62 and YAP were increased in the cartilage of OA models. Notably, knocking down the level of YAP could obviously decrease the inflammation level and alleviate the cartilage degeneration. Recent research indicated that YAP influenced the progression of OA through inhibiting the NF-κB pathway. Here, we confirmed for the first time that YAP could interact with RIPK1 to activate downstream NF-κB signaling pathways. More importantly, we found that LIPUS could restore the impaired capacity of autophagy, decrease the level of YAP and lessen the binding between YAP and RIPK1, thus delay the progression of OA. Our study revealed the specific mechanism of how LIPUS delayed the development of OA, providing a novel therapeutic regimen for OA.