OBJECTIVE: Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption. We investigated synovial tissue expression of the main proteolytic enzymes (MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloprotease 1 (TIMP-1) in juvenile idiopathic arthritides (JIA). METHODS: Expression of MMP-1, MMP-3, MMP-13, and TIMP-1 was studied by immunohistochemical analysis of synovial tissues, obtained at synoviectomy or arthroplasty from 9 patients with JIA, and was correlated with mononuclear cell infiltration into the lining layer. RESULTS: MMP-1 and MMP-3 were abundantly expressed in the lining layer, showing a high degree of correlation with macrophage infiltration (CD68+ cells). MMP-13 showed a lower degree of expression, with tissue distribution almost restricted to the sublining regions. TIMP-1 tissue distribution was similar to that observed for MMP-1 and -3, although with a definitely lower number of positive cells. CONCLUSION: The expression of MMP-1 and MMP-3 in the synovium of patients with IA was clearly correlated with the degree of inflammation. This indicates the possible role of MMP in the pathogenesis of synovitis in this group of pediatric idiopathic arthritides. Inadequate expression of tissue inhibitors may represent a crucial event for the development and perpetuation of tissue damage.
OBJECTIVE: Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption. We investigated synovial tissue expression of the main proteolytic enzymes (MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloprotease 1 (TIMP-1) in juvenile idiopathic arthritides (JIA). METHODS: Expression of MMP-1, MMP-3, MMP-13, and TIMP-1 was studied by immunohistochemical analysis of synovial tissues, obtained at synoviectomy or arthroplasty from 9 patients with JIA, and was correlated with mononuclear cell infiltration into the lining layer. RESULTS:MMP-1 and MMP-3 were abundantly expressed in the lining layer, showing a high degree of correlation with macrophage infiltration (CD68+ cells). MMP-13 showed a lower degree of expression, with tissue distribution almost restricted to the sublining regions. TIMP-1 tissue distribution was similar to that observed for MMP-1 and -3, although with a definitely lower number of positive cells. CONCLUSION: The expression of MMP-1 and MMP-3 in the synovium of patients with IA was clearly correlated with the degree of inflammation. This indicates the possible role of MMP in the pathogenesis of synovitis in this group of pediatric idiopathic arthritides. Inadequate expression of tissue inhibitors may represent a crucial event for the development and perpetuation of tissue damage.
Authors: Sylvia Kamphuis; Kolbrún Hrafnkelsdóttir; Mark R Klein; Wilco de Jager; Margje H Haverkamp; Jolanda H M van Bilsen; Salvatore Albani; Wietse Kuis; Marca H M Wauben; Berent J Prakken Journal: Arthritis Res Ther Date: 2006 Impact factor: 5.156