title: MicroRNA-9 regulates survival of chondroblasts and cartilage integrity by targeting protogenin.
abstract: BACKGROUND
  Studies have shown the roles of miR-9 and its validated target, protogenin (PRTG) in the differentiation of chondroblasts to chondrocyte and in the pathogenesis of osteoarthritis (OA). We hypothesized that miR-9 plays a distinct role in endochondral ossification and OA pathogenesis and the present study was undertaken to identify this role. In the studies, chondroblasts were isolated from limb bud of chick and mouse embryos and articular chondrocytes were isolated from rabbit and human cartilage. Osteoarthritic chondrocytes were isolated from cartilage from patients undergoing total knee replacement. Using these cells, we analyzed the changes in the expression of genes and proteins, tested the expression level of miR-9, and applied a target validation system. We also performed functional study of miR-9 and PRTG.
  
  
  RESULTS
  With the progression of chondrogenesis, decreased miR-9 level was observed at the time of numerous apoptotic cell deaths. And chondrocytes isolated from normal human articular cartilage expressed miR-9, and this expression was significantly reduced in OA chondrocytes, especially decreased its expression in parallel with the degree of cartilage degradation. Over-expression of PRTG induced the activation of caspase-3 signaling and increased apoptosis. However, the co-treatment with the miR-9 precursor or PRTG-specific siRNA blocked this apoptotic signaling.
  
  
  CONCLUSIONS
  This study shows that PRTG is regulated by miR-9, plays an inhibitory action on survival of chondroblasts and articular chondrocytes during chondrogenesis and OA pathogenesis.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, South Korea. jineunjung@wku.ac.kr.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002645:Chickens; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D011817:Rabbits
chemical_list: C551804:MIRN9 microRNA, mouse; C541874:MIRN92 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C586510:protogenin, human; C516330:protogenin, mouse