title: MicroRNA-488 regulates zinc transporter SLC39A8/ZIP8 during pathogenesis of osteoarthritis.
abstract: BACKGROUND
  Even though osteoarthritis (OA) is the most common musculoskeletal dysfunction, there are no effective pharmacological treatments to treat OA due to lack of understanding in OA pathology. To better understand the mechanism in OA pathogenesis and investigate its effective target, we analyzed miRNA profiles during OA pathogenesis and verify the role and its functional targets of miR-488.
  
  
  RESULTS
  Human articular chondrocytes were obtained from cartilage of OA patients undergoing knee replacement surgery and biopsy samples of normal cartilage and the expression profile of miRNA was analyzed. From expression profile, most potent miR was selected and its target and functional role in OA pathogenesis were investigated using target validation system and OA animal model system. Among miRNAs tested, miR-488 was significantly decreased in OA chondrocytes Furthermore, we found that exposure of IL-1β was also suppressed whereas exposure of TGF-β3 induced the induction of miR-488 in human articular chondrocytes isolated from biopsy samples of normal cartilages. Target validation study showed that miR-488 targets ZIP8 and suppression of ZIP8 in OA animal model showed the reduced cartilage degradation. Target validation study showed that miR-488 targets ZIP8 and suppression of ZIP8 in OA animal model showed the reduced cartilage degradation.
  
  
  CONCLUSIONS
  miR-488 acts as a positive role for chondrocyte differentiation/cartilage development by inhibiting MMP-13 activity through targeting ZIP-8.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, South Korea.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053782:Transforming Growth Factor beta3 / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D053583:Interleukin-1beta; C561403:MIRN488 microRNA, human; D035683:MicroRNAs; C530151:SLC39A8 protein, human; D053782:Transforming Growth Factor beta3; D053509:Matrix Metalloproteinase 13