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Exosomal miRNA-486-5p derived from rheumatoid arthritis fibroblast-like synoviocytes induces osteoblast differentiation through the Tob1/BMP/Smad pathway

Jie Chen, Mao Liu, Xiao Luo, Lihui Peng, Zixia Zhao, Chengsong He, Yue He
Biomaterials science 2020 v.8 no.12 pp. 3430-3442
alizarin, biocompatible materials, coculture, collagen, disease severity, exosomes, mice, microRNA, osteoblasts, pathogenesis, patients, rheumatoid arthritis
The pathogenesis of rheumatoid arthritis (RA) is related to the inhibition of osteoblast differentiation. Exosomes secreted from RA fibroblast-like synoviocytes (RA-FLSs-exos) are associated with the pathogenesis of RA and microRNAs (miRNAs) being crucial for RA progression. Accordingly, the aim of the present study is to elucidate the effect of RA-FLS-derived exosomes on osteoblast differentiation and further identify exosomal cargos responsible for this effect. RA-FLSs were isolated from a RA patient and osteoblasts from the donor bone. Isolated RA-FLSs-exos were co-cultured with osteoblasts. Osteoblast differentiation was evaluated by ALP quantification assays, Alizarin Red S staining, and determining markers of osteoblast activity (Osx, OC, Col1a1 and Dlx2). Collagen induced arthritis (CIA)-induced mouse models were established. RA-FLSs-exo could be phagocytosed by osteoblasts. Elevating the expression of miR-486-5p in RA-FLSs-exo promoted osteoblast differentiation. miR-486-5p targeted Tob1 and activated the BMP/Smad signaling pathway in osteoblasts. In addition, RA-FLSs-exo containing miR-486-5p facilitated osteoblast differentiation by activating the BMP/Smad signaling pathway and repressing Tob1. Moreover, RA-FLSs-exo containing miR-486-5p alleviated the disease severity of RA by decreasing Tob1 expression in CIA-induced mice. To sum up, RA-FLSs-exo carrying miR-486-5p serve as a promoter for osteoblast differentiation in RA, ultimately highlighting a promising competitive new target for RA treatment.