title: Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1.
abstract: Osteoarthritis (OA) is a degenerative disease characterized by deterioration of articular cartilage. Recent studies have demonstrated the importance of some microRNAs in cartilage damage. The aim of this study was to identify and characterize the expression of microRNA-634 (miR-634) in normal and OA chondrocytes, and to determine its role in OA pathogenesis. Human normal and OA chondrocytes obtained from patients were cultured in vitro. Transfection with miR-634 mimic or inhibitor was employed to investigate the effect of miR-634 on chondrocyte survival and matrix synthesis, and to identify miR-634 target. The results indicated that miR-634 was expressed at lower level in high grade OA chondrocyte compared with normal chondrocytes. Overexpression of miR-634 could inhibit cell survival and matrix synthesis in high grade OA chondrocytes. Furthermore, miR-634 targeted PIK3R1 gene that encodes the regulatory subunit 1 of class I PI3K (p85α) and exerted its inhibitory effect on the phosphorylation of Akt, mTOR, and S6 signal molecules in high grade OA chondrocytes. Therefore, the data suggested that miR-634 could suppress survival and matrix synthesis of high grade OA chondrocytes through targeting PIK3R1 gene to modulate the PI3K/Akt/S6 and PI3K/Akt/mTOR/S6 axes, with important implication for validating miR-634 as a potential target for OA therapy.
authors.affiliation: Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.affiliation: Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China.
authors.forename: Shaojie
authors.initials: S
authors.lastname: Wang
authors.affiliation: Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China.
authors.forename: Heguo
authors.initials: H
authors.lastname: Cai
authors.affiliation: Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China.
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Medical School, Xiamen University, Xiamen, Fujian, 361102, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Zhongshan Hospital, Xiamen University, Xiamen, Fujian, 361000, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Xia
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000071116:ADAMTS5 Protein / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D058543:Class Ia Phosphatidylinositol 3-Kinase; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000071116:ADAMTS5 Protein; D053674:Aggrecans; D058543:Class Ia Phosphatidylinositol 3-Kinase; D016326:Extracellular Matrix Proteins; D053509:Matrix Metalloproteinase 13; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C000599270:MIRN-634 microRNA, human; C588001:PIK3R1 protein, human; C546842:MTOR protein, human; C121532:ADAMTS5 protein, human