Moxibustion ameliorates abnormal subchondral bone remodeling by promoting ACSL1-mediated autophagy to degrade NLRP3 in osteoarthritis.

Abstract

Background: Osteoarthritis (OA) is a joint disorder that is characterized, among other features, by abnormal subchondral bone remodeling. Moxibustion, a traditional Chinese medicine treatment, has a long history in the clinical treatment of osteoarthritis and has demonstrated significant efficacy. However, the impact mechanisms of moxibustion on subchondral bone in osteoarthritis have yet to be elucidated.

Purpose: This study investigated the specific effects and mechanisms of moxibustion on abnormal subchondral bone remodeling in OA.

Methods: Anterior cruciate ligament transection (ACLT) surgery was performed on mice to establish an OA model, and moxibustion intervention for 4 weeks. The effects of moxibustion on knee osteoarthritis symptoms and walking ability were assessed by knee joint diameter measurement, von Frey test and footprint analysis. Micro-CT, TEM, immunofluorescence staining, and western blot were used to detect the contact between autophagy-lysosomal pathway and NLRP3 inflammasome in subchondral bone remodeling. Subsequently, proteomic analysis was performed on mouse subchondral bone.

Results: We first discovered that moxibustion intervention effectively reduced inflammation in the subchondral bone, thereby balancing the activities of osteoblasts and osteoclasts. Moxibustion, with its warming and medicinal properties, significantly alleviated pain and swelling and enhanced walking ability in OA mice. The findings also suggested that moxibustion counteracted subchondral bone imbalance by inhibiting the activation of the NLRP3 inflammasome through increased autolysosome levels. Proteomic analysis and experimental validation revealed that moxibustion promoted ACSL1 expression to regulate autophagy in OA subchondral bone.

Conclusion: Our study elucidated the molecular mechanism by which moxibustion improved the inflammatory environment and abnormal subchondral bone remodeling in OA mice by activating ACSL1-mediated autophagy, providing the basis and new insights for  advancing moxibustion therapy in OA.