title: The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses.
abstract: OBJECTIVE
  The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration.
  
  
  METHODS
  miR-381 expression was assessed in vitro in response to IL-1β stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2.
  
  
  RESULTS
  miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1β in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity.
  
  
  CONCLUSIONS
  miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13.
authors.forename: Changhe
authors.initials: C
authors.lastname: Hou
authors.forename: Fangang
authors.initials: F
authors.lastname: Meng
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Kang
authors.forename: Weishen
authors.initials: W
authors.lastname: Chen
authors.forename: Guangxin
authors.initials: G
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Fu
authors.forename: Puyi
authors.initials: P
authors.lastname: Sheng
authors.forename: Ziji
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weiming
authors.initials: W
authors.lastname: Liao
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000235:genetics*; D024043:Collagen Type II / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; D053583:Interleukin-1beta; C588249:MIRN381 microRNA, human; D035683:MicroRNAs; C493709:RUNX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D053509:Matrix Metalloproteinase 13