Involvement of MT1-MMP and TIMP-2 in human periodontal disease

Abstract

OBJECTIVES: Periodontal disease is characterized by an increased collagen metabolism. Although membrane type-1 matrix metalloproteinase (MT1-MMP) plays a critical role in collagen degradation, its involvement in human periodontitis remains to be determined. METHODS: MT1-MMP and TIMP-2 expression and distribution were evaluated in gingival tissue samples derived from 10 healthy and 12 periodontitis-affected human subjects. MT1-MMP and TIMP-2 expression were assessed through Western-blot of tissue homogenates. The main cell types involved in MT1-MMP and TIMP-2 production were evaluated by means of immunohistochemistry. RESULTS: Both MT1-MMP and TIMP-2 were significantly increased in periodontitis-affected gingival tissues when compared to healthy gingiva. Moreover, the balance between MT1-MMP and its inhibitor TIMP-2 was altered in periodontitis-affected tissues, suggesting an imbalance in this proteolytic axis. Immunohistochemistry demonstrated the expression of MT1-MMP in fibroblasts and macrophages in gingival tissues. MT1-MMP was detected in cells in close association with the gingival collagen matrix. TIMP-2 expression was identified in fibroblasts, macrophages and epithelial cells. CONCLUSIONS: Our observations show an increased expression of MT1-MMP and TIMP-2 in periodontitisaffected gingival tissues. The altered balance between these two molecular mediators of collagen remodeling suggests their involvement in human periodontal disease.