title: miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1.
abstract: Tendon stem/progenitor cell (TSPC) senescence may lead to age-related tendon disorders and impair tendon regeneration and replacement capacity in humans. However, the mechanisms governing TSPC aging and degeneration remain obscure. Recently, it has been reported that Rho-associated coiled-coil protein kinase 1 (ROCK1) might be a key player in TSPC aging process. miRNAs are also involved in cellular senescence. In this study, whether miRNAs modulate senescence of TSPCs through targeting ROCK1 was evaluated. We found that miR-135a, which directly binds to the 3'-untranslated region of ROCK1, is significantly downregulated in aged compared with young TSPCs. Overexpression of miR-135a in young TSPCs suppresses senescence, promotes proliferation, and induces migration and tenogenic differentiation, whereas suppression of miR-135a in aged TSPCs has the opposite effects. By gain-of-function and loss-of-function studies, we confirmed that ROCK1 mediates the effects of miR-135a in TSPCs. Taken together, our data suggest that miR-135a plays an important role in TSPC senescence via targeting ROCK1.
authors.affiliation: Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, PR China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Jun-Peng
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, PR China.
authors.forename: Hua-Song
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, PR China.
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, PR China. Electronic address: qingwangchina@163.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, PR China. Electronic address: chinacaixianhua@163.com.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Cai
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000375:Aging / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D016922:Cellular Senescence; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology*; D013710:Tendons / Q000166:cytology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C000600409:MIRN135 microRNA, rat; D035683:MicroRNAs; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases
keywords: Aging; Proliferation; ROCK1; Tendon stem/progenitor cells; miR-135a