Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation: Implications for cartilage degradation in arthritis Journal Articles uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • AbstractObjectiveWe 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.MethodsMMP 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 α (TNFα) 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.ResultsMMP‐10 expression was confirmed in both chondrocytes and synovial fibroblasts following stimulation with either IL‐1 plus OSM or TNFα 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.ConclusionWe 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

  • Barksby, HE
  • Milner, JM
  • Patterson, AM
  • Peake, NJ
  • Hui, W
  • Robson, T
  • Lakey, R
  • Middleton, J
  • Cawston, TE
  • Richards, Carl
  • Rowan, AD

publication date

  • October 2006

has subject area