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

Abstract

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

Exosomes: roles and therapeutic potential in osteoarthritis

“…183,184 • Suppress osteoclast activity in subchondral bone via RANKL-RANK-TRAF6 pathway. 185 • Inhibit proliferation and enhance apoptosis in synovial fibroblasts via microRNA-26a-5p/ PTGS2 pathway. 186 • Reduce the damage of articular cartilage.…”

“…186 • Reduce the damage of articular cartilage. 182,185 • Abrogate the degradation of subchondral bone. 182,185 • Inhibit aberrant nerve invasion and abnormal formation of H-type vessel in subchondral bone.…”

Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model

“…However, BMSCs can also be tumorigenic and are often inappropriately retained by target tissues, limiting their clinical usefulness [9]. Emerging data suggest that BMSCs may promote regeneration in a paracrine/endocrine manner by delivering EVs to specific tissues [8].…”

“…EVs, which are typically approximately 40-200 nm in size [10], can be categorized as exosomes, microvesicles and apoptotic bodies. EVs are membranous bodies that are released by almost all cells [8]. For a long time, EVs were considered to be debris without any biological function.…”

“…BMSCs are generally recognized for their ability to self-renew and differentiate into multiple lineages; however, this can lead to teratoma formation by transplanted BMSCs, which limits their therapeutic effectiveness [8]. Recently it has become increasingly clear that BMSC-derived extracellular vesicles (BMSC-EVs) have important biological functions and molecular mechanisms [9], and may serve as an alternative to therapies based on BMSC transplantation [8]. EVs, which originate from BMSC endosomal compartments, can modulate inflammation [10][11][12].…”