Work

Osteoclast-derived apoptotic bodies accelerate the pathological progression of osteoarthritis via disturbing subchondral bone remodeling

Year: 2025

Type: article

Abstract: Objective: To investigate the role of osteoclast-derived apoptotic bodies (OC-ABs) in osteoarthritis (OA), specifically their impact on subchondral bone remodeling and disease progression, and to explore potential therapeutic strategies targeting OC-AB-induced pathways. Methods: We utilized a mouse model of anterior cruciate ligament transection (ACLT) to simulate post-traumatic osteoarthritis (PTOA). Levels of OC-ABs were assessed in subchondral bone and correlated with OA severity. Additionally, apoptotic body-deficient MRL/lpr mice were analyzed to evaluate the direct contribution of OC-ABs to OA progression and subchondral bone remodeling. The involvement of OC-ABs in osteogenesis was further examined using mesenchymal stem cells (MSCs), with a focus on the RANKL reverse signaling pathway. The therapeutic potential of rapamycin to counteract OC-AB effects was tested. Results: Increased OC-AB accumulation in subchondral bone was positively correlated with OA severity in ACLT-induced mice. Apoptotic body-deficient MRL/lpr mice demonstrated slower OA progression and maintained more stable subchondral bone architecture, indicating a pathogenic role of OC-ABs in OA. OC-ABs significantly stimulated osteogenesis in MSCs via the RANKL reverse signaling pathway. Treatment with rapamycin effectively reversed OC-AB-induced subchondral bone formation, mitigated OA progression, and inhibited the RANKL reverse signaling pathway. Conclusion: OC-ABs play a critical role in exacerbating OA by promoting subchondral bone remodeling via the RANKL reverse signaling pathway. Rapamycin presents as a promising therapeutic agent capable of mitigating OC-AB-driven pathology, highlighting new avenues for targeted OA treatment.

Source: Journal of Orthopaedic Translation

DOI: 10.1016/j.jot.2025.01.004