title: MiR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis.
abstract: Osteoarthritis (OA) is characterized by degradation of articular cartilage and joint inflammation. MicroRNAs have been proved to play an important role in the regulation of chondrogenesis. Previous study showed that microRNA-210 (miR-210) was probably associated with osteoarthritis, while the function of miR-210 in osteoarthritis still remains unknown. The aim of the present study was to investigate the protective effect of miR-210 on osteoarthritis. In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS). Transfection with miR-210 mimic inhibited LPS-induced pro-inflammatory cytokines production, cell viability reduction and cell apoptosis. Results of luciferase activity assay showed that miR-210 targeted 3'-UTR of death receptor 6 (DR6) to inhibit its expression. MiR-210 mimic and DR6 siRNA transfection inhibited the activation of NF-κB pathway and cell apoptosis of chondrocytes. For the in vivo study, OA model was established on rats by anterior cruciate ligament transection (ACLT). MiR-210 expression is reduced in OA rats. MiR-210 over-expressing lentivirus was injected into the OA rats. Cytokines production, and NF-κB and DR6 expression in OA rats was inhibited by miR-210 overexpression. The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Guangyue
authors.initials: G
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D008070:Lipopolysaccharides; C546388:MIRN210 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor