title: Effects of miR-145 on the inhibition of chondrocyte proliferation and fibrosis by targeting TNFRSF11B in human osteoarthritis.
abstract: Osteoarthritis (OA) is a common cause of functional deterioration in older adults, and altered chondrogenesis is the most common pathophysiological process involved in the development of OA. MicroRNA‑145 (miR‑145) has been shown to regulate chondrocyte homeostasis. However, the function of miR‑145 in OA remains to be elucidated. In the present study, the expression levels of miR‑145 were examined in cartilage specimens from 25 patients with knee OA using reverse transcription‑quantitative polymerase chain reaction analysis. The effects of miR‑145 on the proliferation and fibrosis of the C‑20/A4 and CH8 cell lines were also investigated using 3-(4,5-dimethylth-iazol-2-yl)-2,5-diphenyltetrazolium bromide and western blot assays in vitro. The results revealed that the expression of miR-145 was decreased in the OA cartilage tissues, compared with normal cartilage tissues. The overexpression of miR‑145 by transfection of cells with miR‑145 mimics significantly inhibited C‑20/A4 and CH8 cell proliferation and fibrosis. Furthermore, tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) was identified as a direct target of miR‑145 in chondrocytes, which was confirmed using a dual‑luciferase reporter assay. The expression level of TNFRSF11B was markedly upregulated in the patients with OA, and the ectopic expression of miR‑145 was capable of suppressing the expression of TNFRSF11B. In addition, the knock down of TNFRSF11B using specific small interfering RNA also inhibited the proliferation and fibrosis of C‑20/A4 and CH8 cells in vitro. These data provide the first evidence, to the best of our knowledge, to suggest the critical function of miR‑145 in regulating the expression of TNFRSF11B, which may have important implications on the regulation of chondrocyte proliferation and fibrosis in OA.
authors.affiliation: Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
authors.forename: Yu-Ge
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
authors.forename: Shuai-Shuai
authors.initials: SS
authors.lastname: Niu
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
authors.forename: Long-Fei
authors.initials: LF
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China.
authors.forename: Yuan-Min
authors.initials: YM
authors.lastname: Zhang
mesh_terms: D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000473:pathology*; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology*; D053244:Osteoprotegerin / Q000235:genetics*
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human