title: MicroRNA-93 regulates collagen loss by targeting MMP3 in human nucleus pulposus cells.
abstract: OBJECTIVE
  Degenerated disc disease is one of the most common medical conditions in patients suffering from low back pain. Recent studies have shown that microRNAs can regulate cell function in many pathological conditions. The aim of this study was to investigate expression and role of miR-93 in disc degeneration.
  
  
  METHODS
  Quantitative RT-PCR was employed to investigate level of miR-93 in degenerative nucleus pulposus (NP) tissues. Then, functional analysis of miR-93 in regulating collagen II expression was performed. Subsequently, western blotting and luciferase reporter assay were used to detect the target gene.
  
  
  RESULTS
  We showed that miR-93 was significantly down-regulated in degenerative NP tissues and its levels were associated with grade of disc degeneration. Overexpression of miR-93 stimulated type II collagen expression in NP cells. Moreover, MMP3 was identified as a putative target of miR-93. MiR-93 inhibited MMP3 expression by directly targeting its 3'UTR, and this was abolished by miR-93 binding site mutations. Additionally, restoration of MMP3 in miR-93-overexpressed NP cells reversed effects of type II collagen expression. Expression of MMP3 inversely correlated with miR-93 expression in degenerative NP tissues.
  
  
  CONCLUSIONS
  Taken together, we demonstrated that miR-93 contributed to abnormal NP cell type II collagen expression by targeting MMP3, involved in intervertebral disc degeneration.
authors.affiliation: Department of Orthopaedics, Tianjin First Central Hospital, Tianjin, 300192, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Jing
authors.forename: Wenxue
authors.initials: W
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001665:Binding Sites; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D024043:Collagen Type II; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
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