title: Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model.
abstract: BACKGROUND
  Rheumatoid arthritis is an autoimmune disease in which joint inflammation leads to progressive cartilage and bone erosion. Matrix metalloproteinases (MMPs) implicated in homeostasis of the extracellular matrix play a central role in cartilage degradation. However, the role of specific MMPs in arthritis pathogenesis is largely unknown. The aim of the present study was to investigate the role of Mmp-8 (collagenase-2) in an arthritis model.
  
  
  METHODS
  Arthritis was induced in Mmp8-deficient and wildtype mice by K/BxN serum transfer. Arthritis severity was measured by a clinical index and ankle sections were scored for synovial inflammation, cartilage damage and bone erosion. cDNA microarray analysis, real-time PCR and western blot were performed to identify differential changes in gene expression between mice lacking Mmp8 and controls.
  
  
  RESULTS
  Mmp8 deficiency increased the severity of arthritis, although the incidence of disease was similar in control and deficient mice. Increased clinical score was associated with exacerbated synovial inflammation and bone erosion. We also found that the absence of Mmp8 led to increased expression of IL-1β, pentraxin-3 (PTX3) and prokineticin receptor 2 (PROKR2) in arthritic mice joints.
  
  
  CONCLUSIONS
  Lack of Mmp-8 is accompanied by exacerbated synovial inflammation and bone erosion in the K/BxN serum-transfer arthritis model, indicating that this Mmp has a protective role in arthritis.
authors.affiliation: Research Laboratory and Rheumatology Unit, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Biomedical Research Institute (IDIS), Travesia da Choupana s/n, Santiago de Compostela, 15706 A Coruña, Spain.
authors.forename: Samuel
authors.initials: S
authors.lastname: García
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Forteza
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otin
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gómez-Reino
authors.forename: Antonio
authors.initials: A
authors.lastname: González
authors.forename: Carmen
authors.initials: C
authors.lastname: Conde
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000473:pathology; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D015153:Blotting, Western; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D020784:Matrix Metalloproteinase 8 / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020784:Matrix Metalloproteinase 8