BMSCs‐Derived Exosomes Ameliorate Pain Via Abrogation of Aberrant Nerve Invasion in Subchondral Bone in Lumbar Facet Joint Osteoarthritis

Lumbar facet joint osteoarthritis (LFJ OA) is regarded as one of the common causes of low back pain (LBP). The pathogenesis and underlying mechanism of this disease are largely unknown, there is still no effective disease‐modifying therapy. This study aims to investigate the efficacy of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the pathogenesis and behavioral signs of LBP in the LFJ OA mouse model. The pathogenetic change in cartilage and aberrant nerve invasion in the subchondral bone of LFJ in a mouse model after treatment with BMSC‐exosomes was evaluated. BMSC‐exosomes could relieve pain via abrogation of aberrant CGRP‐positive nerve and abnormal H‐type vessel formation in the subchondral bone of LFJ. Moreover, BMSC‐exosomes attenuated cartilage degeneration and inhibited tartrate‐resistant acid phosphatase expression and RANKL‐RANK‐TRAF6 signaling activation to facilitate subchondral bone remodeling. These results indicated that BMSC‐exosomes could relive behavioral signs of LBP and pathological processes in LFJ OA. BMSC‐exosomes have a prominent protective effect and might be a potential therapeutic option for the treatment of LFJ OA causing LBP. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:670–679, 2020