title: MicroRNA-30a promotes extracellular matrix degradation in articular cartilage via downregulation of Sox9.
abstract: OBJECTIVE
  Sox9 has recently been reported to be a key mediator during cartilage degradation in osteoarthritis (OA). Our aim was to clarify the role of microRNA-30a (miR-30a) and its target gene Sox9 in regulation of extracellular matrix (ECM) degradation in OA.
  
  
  METHODS
  Expression of miR-30a in cartilage tissues and in primary chondrocytes from healthy and OA donors, was determined by real-time PCR, and levels of Sox9 mRNA and protein were analyzed by real-time PCR and western blotting, respectively. Subsequently, the target of miR-30a was predicted by bioinformatics and confirmed using a luciferase assay. Expression of ECM-related genes was determined by tissue-specific staining, immunofluorescence, real-time PCR, and western blotting. The role of miR-30a in OA was examined in vivo using a collagenase-induced OA rat model.
  
  
  RESULTS
  miR-30a was significantly upregulated and Sox9 was downregulated in primary chondrocytes from cartilage taken from OA donors compared to healthy controls. We showed that miR-30a specifically bound to the 3' UTR of Sox9, and overexpression of miR-30a downregulated expression levels of Sox9, proteoglycan aggrecan, and Col II compared to those induced by small interfering RNA transfection to knockdown Sox9. miR-30a inhibition reversed the effects of ECM degradation in vitro and in vivo.
  
  
  CONCLUSIONS
  miR-30a acts as a virulence MRA in OA, promoting ECM degradation by targeting Sox9 and by modulating activity of its downstream effectors Col II and proteoglycan aggrecan.
authors.affiliation: Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.|Department of Orthopedics, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi, 046000, China.
authors.forename: Tingjie
authors.initials: T
authors.lastname: Chang
authors.affiliation: Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi, 046000, China.
authors.forename: Hongzhuo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi, 046000, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.|Department of oncology, Peace Hospital of Changzhi Medical College, Changzhi 046000, PR, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
authors.forename: Yihe
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D010003:Osteoarthritis / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D055758:SOX9 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053674:Aggrecans; C508585:IL1B protein, human; D053583:Interleukin-1beta; C556157:MIRN30 microRNA, rat; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D003094:Collagen