title: Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation: implications for cartilage degradation in arthritis.
abstract: OBJECTIVE
  We have previously reported the up-regulation of matrix metalloproteinase 10 (MMP-10) following treatment with the procatabolic stimulus of interleukin-1 (IL-1) and oncostatin M (OSM) in chondrocytes. Although MMP-10 is closely related to MMP-3, little is known about the role of MMP-10 in cartilage catabolism. The purpose of this study was to determine whether MMP-10 is expressed in connective tissue cells and to assess how it may contribute to cartilage collagenolysis.
  
  
  METHODS
  MMP gene expression was assessed by real-time polymerase chain reaction using RNA from human articular chondrocytes and synovial fibroblasts stimulated with IL-1 plus OSM or tumor necrosis factor alpha (TNFalpha) plus OSM. Synovial fluid levels of MMP-10 were determined by specific immunoassay. Recombinant procollagenases were used in activation studies. Immunohistochemistry assessed MMP-10 expression in diseased joint tissues.
  
  
  RESULTS
  MMP-10 expression was confirmed in both chondrocytes and synovial fibroblasts following stimulation with either IL-1 plus OSM or TNFalpha plus OSM, and MMP-10 was detected in synovial fluid samples from patients with various arthropathies. Exogenous MMP-10 significantly enhanced collagenolysis from IL-1 plus OSM-stimulated cartilage, and MMP-10 activated proMMP-1, proMMP-8, and proMMP-13. Immunohistochemistry revealed the presence of MMP-10 in the synovium and cartilage of an IL-1 plus OSM-induced model of arthritis as well as in samples of diseased human tissues.
  
  
  CONCLUSIONS
  We confirm that both synovial fibroblasts and articular chondrocytes express MMP-10 following treatment with procatabolic stimuli. Furthermore, the detectable levels of synovial fluid MMP-10 and the histologic detection of this proteinase in diseased joint tissues strongly implicate MMP-10 in the cartilage degradome during arthritis. The ability of MMP-10 to superactivate procollagenases that are relevant to cartilage degradation suggests that this activation represents an important mechanism by which this MMP contributes to tissue destruction in arthritis.
authors.affiliation: School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, UK.
authors.forename: H E
authors.initials: HE
authors.lastname: Barksby
authors.forename: J M
authors.initials: JM
authors.lastname: Milner
authors.forename: A M
authors.initials: AM
authors.lastname: Patterson
authors.forename: N J
authors.initials: NJ
authors.lastname: Peake
authors.forename: W
authors.initials: W
authors.lastname: Hui
authors.forename: T
authors.initials: T
authors.lastname: Robson
authors.forename: R
authors.initials: R
authors.lastname: Lakey
authors.forename: J
authors.initials: J
authors.lastname: Middleton
authors.forename: T E
authors.initials: TE
authors.lastname: Cawston
authors.forename: C D
authors.initials: CD
authors.lastname: Richards
authors.forename: A D
authors.initials: AD
authors.lastname: Rowan
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism*; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D053683:Oncostatin M / Q000494:pharmacology; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D004792:Enzyme Precursors; D006131:Growth Inhibitors; D007375:Interleukin-1; D053683:Oncostatin M; D003094:Collagen; D017364:Collagenases; C022440:procollagenase; D053506:Matrix Metalloproteinase 10; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1