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Journal of Dental Research
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Human Neutrophil Collagenase MMP-8 in Peri-implant Sulcus Fluid and its Inhibition by Clodronate

O. Teronen

Department of Oral and Maxillofacial Surgery, Institute of Dentistry, P.O. Box 41, FIN-00014 University of Helsinki, Finland, Department of Oral and Maxillofacial Surgery, Department of Surgery, University of Helsinki

Y.T. Konttinen

Department of Medicine and Department of Anatomy, University of Helsinki

C. Lindqvist

Department of Oral and Maxillofacial Surgery, Institute of Dentistry, P.O. Box 41, FIN-00014 University of Helsinki, Finland, Department of Oral and Maxillofacial Surgery, Department of Surgery, University of Helsinki

T. Salo

Departments of Oral and Maxillofacial Surgery and Pathology, University of Oulu

T. Ingman

Department of Pedodontics and Orthodontics, Institute of Dentistry, University of Helsinki

A. Lauhio

Department of Medical Chemistry, University of Helsinki

Y. Ding

Department of Periodontology, Institute of Dentistry, University of Helsinki

S. Santavirta

Department of Orthopedics and Traumatology, Department of Surgery, University of Helsinki

T. Sorsa

Department of Periodontology, Institute of Dentistry, University of Helsinki, Department of Medical Chemistry, University of Helsinki

The exact molecular mechanisms of the loosening of a dental implant are not well-known. The characteristics of implant sulci are similar to those of periodontal sulci regarding gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF). Proteolytic enzymes, matrix metalloproteinases (MMPs), participate in peri-implant tissue remodeling. Clodronate is a well-tolerated bisphosphonate-group drug currently used in bone-resorption-related diseases in humans. The mechanisms of bisphosphonate action are not clarified. Collagenase activity in diseased PISF was significantly higher than in the clinically healthy group. Immunoblotting disclosed that diseased PISF contained increased immunoreactives MMP-8 compared with the healthy PISF. The residual latent collagenase activity in the diseased PISF was activated by gold thioglucose and inhibited completely by 100 pM of doxycycline closely resembling pure neutrophil collagenase (MMP-8). The presence of MMP-8 in diseased but not in clinically healthy PISF may prove to be a useful biochemical indicator to monitor peri-implant health and disease. Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 uM of clodronate), an osteoactive, antiresorptive bisphosphonate. Furthermore, the new finding suggests an extended and hitherto-undescribed potential for clodronate in preventing the loosening of both implants and teeth, based on a dual beneficial effect: prevention of both bone resorption/osteolysis and of soft tissue/dental ligament destruction. Potential new therapeutic indications based on the collagenase-inhibiting effect of clodronate provide potential new therapeutic indications for a variety of diseases involving connective tissue breakdown, such as periodontal disease, arthritides, and tumor invasion.

Key Words: metalloproteinases • clodronate/bisphosphonates • inhibition • gingival crevicular fluid • peri-implant sulcus fluid.

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Journal of Dental Research, Vol. 76, No. 9, 1529-1537 (1997)
DOI: 10.1177/00220345970760090401
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