Gerd-Jan Boelen1, Lucas Boute1, Joëy d'Hoop1, Mostafa EzEldeen1,2, Ivo Lambrichts3, Ghislain Opdenakker4,5. 1. Department of Oral Health Sciences, KU Leuven, Leuven, Belgium. 2. OMFS-IMPATH Research Group, Faculty of Medicine, Department of Imaging and Pathology, Oral and Maxillofacial Surgery, KU Leuven, Leuven, Belgium. 3. Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium. 4. Department of Oral Health Sciences, KU Leuven, Leuven, Belgium. ghislain.opdenakker@rega.kuleuven.be. 5. Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, KU Leuven, Herestraat 49, Box 1044, 3000, Leuven, Belgium. ghislain.opdenakker@rega.kuleuven.be.
Abstract
OBJECTIVES: Matrix metalloproteinase (MMP) expression has been associated with tissue development, invasive cancer cell behavior, and inflammation. The associations of increased expression of MMPs with diseases have led to intensive research activities to develop MMP inhibitors. Here, the questions are addressed which associations between increased levels of any MMP with dental diseases may be cause or consequence, whether MMP levels may be of diagnostic value and whether and which MMP inhibitors need further investigations for use in dental diseases. METHODS: To study the role of MMPs and to discriminate between cause or consequence, the literature about measurements of MMPs and about the use of inhibitory drugs and genetic knockout animal models in dentistry was compared. RESULTS: The only FDA-approved treatment with MMP inhibitors is tetracyclines for periodontitis, whereas a diagnostic test for activated MMP-8 in oral fluids is valued in practical periodontology. The MMP literature in dentistry is artificially skewed to the gelatinases MMP-2 and MMP-9 and to enamelysin, alias MMP-20. The basis for this observation is, respectively, the widely used and sensitive technique of gelatin zymography and enamel proteins as substrates of MMP-20. Studies on additional MMPs are gaining interest in dentistry and MMP inhibitors may provide new applications. In addition, drugs with proven effects for the treatment of dental diseases may be found to act through MMP inhibition. CONCLUSION AND RELEVANCE: In conclusion, research on MMPs and inhibitors may provide practical applications beyond diagnosis and treatment of periodontitis and will be, directly or indirectly, beneficial for patients with dental or periodontal diseases.
OBJECTIVES: Matrix metalloproteinase (MMP) expression has been associated with tissue development, invasive cancer cell behavior, and inflammation. The associations of increased expression of MMPs with diseases have led to intensive research activities to develop MMP inhibitors. Here, the questions are addressed which associations between increased levels of any MMP with dental diseases may be cause or consequence, whether MMP levels may be of diagnostic value and whether and which MMP inhibitors need further investigations for use in dental diseases. METHODS: To study the role of MMPs and to discriminate between cause or consequence, the literature about measurements of MMPs and about the use of inhibitory drugs and genetic knockout animal models in dentistry was compared. RESULTS: The only FDA-approved treatment with MMP inhibitors is tetracyclines for periodontitis, whereas a diagnostic test for activated MMP-8 in oral fluids is valued in practical periodontology. The MMP literature in dentistry is artificially skewed to the gelatinases MMP-2 and MMP-9 and to enamelysin, alias MMP-20. The basis for this observation is, respectively, the widely used and sensitive technique of gelatin zymography and enamel proteins as substrates of MMP-20. Studies on additional MMPs are gaining interest in dentistry and MMP inhibitors may provide new applications. In addition, drugs with proven effects for the treatment of dental diseases may be found to act through MMP inhibition. CONCLUSION AND RELEVANCE: In conclusion, research on MMPs and inhibitors may provide practical applications beyond diagnosis and treatment of periodontitis and will be, directly or indirectly, beneficial for patients with dental or periodontal diseases.
Authors: Jialiang Hu; Philippe E Van den Steen; Qing-Xiang A Sang; Ghislain Opdenakker Journal: Nat Rev Drug Discov Date: 2007-06 Impact factor: 84.694
Authors: Don Jeevanie Epasinghe; Cynthia Kar Yung Yiu; Michael Francis Burrow; Noriko Hiraishi; Franklin Russell Tay Journal: J Dent Date: 2013-06-24 Impact factor: 4.379