BMSC-derived exosomes from congenital polydactyly tissue alleviate osteoarthritis by promoting chondrocyte proliferation

Abstract

In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and exosomes may play a major role. Here, we acquired a special kind of MSCs from the bone marrow of surgically resected tissue from the hand of a patient with polydactyly. Experiments were focused on the role of polydactyly bone marrow-derived MSCs (pBMSCs) in osteoarthritis. The results showed that the pBMSCs had a greater ability than the BMSCs to differentiate into chondrocytes. Mechanistically, the expression of BMP4 was significantly higher in the pBMSCs than it was in the BMSCs. Furthermore, we showed that the migration and proliferation of chondrocytes were stimulated by exosomes secreted by pBMSC (pBMSC-EXOs). Notably, the downregulation of BMP4 in pBMSCs by siRNA inhibited both the chondrogenic differentiation potential of the MSCs and the function of the chondrocytes. In addition, the injection of pBMSC-EXOs and BMSC-EXOs attenuated OA in an OA mouse model, but the pBMSC-EXOs had a superior therapeutic effect compared with that of the BMSC-EXOs. Taken together, the data indicate that pBMSCs have greater ability to differentiate into chondrocytes and regulate chondrocyte formation through BMP4 signaling. Therefore, pBMSC-EXOs may represent a novel treatment for OA.

Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320

“…The dehydrated specimens were embedded in paraffin. Furthermore, the 5 μm thickness and stained with safranin O/fast green (Zhou et al 2020 ). The severity of OA lesions was classified by two independent researchers, according to the Osteoarthritis Research Society International (OARSI) cartilage assessment system (Chen et al 2017 ).…”

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

“…Injection of pBMSC-EVs and BMSC-EVs reduced OA in the OA mouse model, but compared with BMSC-EVs, pBMSC-EVs had a better therapeutic effect. Therefore, pBMSC-EVs may represent a new OA treatment method [ 32 ].…”

“…Besides, the expression of collagen X and runx2 decreased, while the expression of collagen II and sox9 increased. Zhang et al, 2020 [ 30 ] pBMMSC Human chondrocytes Cells treated with 1, 5, or 10 µg/mL EVs for 24 h. EVs enhanced chondrocyte migration and proliferation Zhou et al, 2020 [ 32 ] ADSC Human chondrocytes Cells treated with 1, 5 and 10 × 10 8 particles/mL EVs for 24 h. EVs enhanced the expression of anabolic marker collagen II and decreased the expression of catabolic marker MMP13 and ADAMTS5. EVs can significantly increase the autophagy level of chondrocytes partially through mTOR inhibition.…”

“… The mice were injected with pBMSC-EVs on days 7, 14 and 21, respectively. pBMSC-EVs can reduce cartilage damage caused by OA Zhou et al, 2020 [ 32 ] ADSC Surgical destabilization of the medial meniscus (DMM). The mice were given multiple intra-articular injections of 10 μL EVs (10 10 particles/mL) for 4 weeks (twice a week).…”

Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases

“…He et al reported that BM-MSCs-Exos alleviated the inhibitory effect of IL-1β on the proliferation and migration of chondrocytes and redressed the imbalance of matrix anabolism in vitro , and downregulated calcitonin gene-related peptide (CGRP) and iNOS in the dorsal root ganglion (DRG) tissue of sodium iodoacetate-induced rat model, consequently reducing the pain response (He et al, 2020a ). In another experiment, Zhou et al acquired a special kind of exosomes from polydactyly bone marrow-derived MSCs (pBMSCs-Exos), which showed an improved therapeutic effect compared to BM-MSCs-Exos by regulating chondrogenesis via a BMP4 signal pathway in an OA mouse model (Zhou X. et al, 2020 ). Collectively, these results suggested that BM-MSCs-Exos might treat OA by promoting the proliferation and migration of chondrocytes.…”