Expression of Cathepsin K in Periodontitis

Objectives: Gingival crevicular fluid (GCF) in periodontitis contains high cathepsin K concentrations correlating with the active sites/clinical parameters and decreasing after scaling and root planning. Due to positive correlations between cathepsin K and receptor activator of nuclear factor kappa B ligand (and alveolar bone loss), GCF-cathepsin K has been taken as a biomarker of osteoclasts. We hypothesized that cells other than osteoclasts could contribute to the GCF-cathepsin K. Methods: Local ethical committee approved the study. Cathepsin K IgG was used to immunostain formalin fixed paraffin embedded human periodontal tissues. Ten healthy (age range 30-37 years) and ten periodontitis (age range 31-45 years) patient samples were used. The influence of TNF-α on fibroblast-mediated cathepsin K release was studied with western blot. Student’s t-test was used to compare data between tissues or cultured fibroblasts. Results: Macrophage-like cells, fibroblast-like cells, vascular endothelial cells and gingival epithelial cells were more intensively stained for cathepsin K and also more frequent in periodontitis (665±104 vs. 258±40 cells/mm², p < 0.01). Resting fibroblasts released 2-3-fold more 43 kD pro-cathepsin K than 29 kD active cathepsin K. Stimulation of fibroblasts with TNF-α increased the release of the activated cathepsin K 4-5-fold. Conclusion: Results suggest that GCF-cathepsin K is not only osteoclast-derived, but in periodontitis other cells contribute to it. GCF-cathepsin K, perhaps together with intracellular, lysosomal collagenolytically active cathepsin K in fibroblasts, macrophages and gingival epithelial cells, can contribute to the loss of attachment and destruction of the periodontal ligament.