HUMAN NEUTROPHIL COLLAGENASE MMP-8 IN PERI-IMPLANT SULCUS FLUID AND ITS INHIBITION BY CLODRONATE

The exact molecular mechanisms of the loosening of a dental implant ar e not well-known. The characteristics of implant sulci are similar to those of periodontal sulci regarding gingival crevicular fluid (GCF) a nd peri-implant sulcular fluid (PISF). Proteolytic enzymes, matrix met alloproteinases (MMPs), participate in peri-implant tissue remodeling. Clodronate is a well-tolerated bisphosphonate-group drug currently us ed in bone-resorption-related diseases in humans. The mechanisms of bi sphosphonate action are not clarified. Collagenase activity in disease d PISF was significantly higher than in the clinically healthy group. Immunoblotting disclosed that diseased PISF contained increased immuno reactives MMP-8 compared with the healthy PISF. The residual latent co llagenase activity in the diseased PISF was activated by gold thiogluc ose and inhibited completely by 100 mu M of doxycycline closely resemb ling pure neutrophil collagenase (MMP-8). The presence of MMP-8 in dis eased but not in clinically healthy PISF may prove to be a useful bioc hemical indicator to monitor peri-implant health and disease. Pure hum an neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth w ere efficiently inhibited in vitro by clodronate (50% inhibition [IC50 ] was achieved by 150 mu M of clodronate), an osteoactive, antiresorpt ive bisphosphonate. Furthermore, the new finding suggests an extended and hitherto-undescribed potential for clodronate in preventing the lo osening of both implants and teeth, based on a dual beneficial effect: prevention of both bone resorption/osteolysis and of soft tissue/dent al ligament destruction. Potential new therapeutic indications based o n the collagenase-inhibiting effect of clodronate provide potential ne w therapeutic indications for a variety of diseases involving connecti ve tissue breakdown, such as periodontal disease, arthritides, and tum or invasion.