Periodontal Disease, Matrix Metalloproteinases and Chemically Modified Tetracyclines
- Publisher: Microbial Ecology in Health and Disease
Microbial Ecology in Health and Disease
(issn: 1651-2235, eissn: 1651-2235)
Matrix metalloproteinases (MMPs) are crucial in the degradation of the main components in the extracellular matrix and thereby play important roles in cell migration, wound healing and tissue remodelling. MMPs have pathogenic roles in arthritis, periodontitis, hepatitis, glomerulonephritis, atherosclerosis and cancer cell invasion. MMPs are activators of pro-inflammatory mediators that occur in latent forms, such as interleukin (IL)-1β, membrane-bound tumour necrosis factor (TNF) and different MMPs. To regulate their action, MMPs are secreted in latent, inactive pro-enzyme forms, with plasmin and other MMPs as likely activators. MMP activity is further modulated by the tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4), which partly control and stabilize MMPs. In normal steady-state tissues, only low levels of MMPs are detected intra- and extra-cellularly because MMPs are tightly regulated at the level of transcription and secretion. In inflamed periodontal tissue, numbers of cells expressing MMPs are increased as compared with healthy gingival tissue. Recently, novel nonantimicrobial MMP-inhibitory effects of tetracyclines were discovered, and subsequently a panel of chemically modified non-antimicrobial tetracyclines (CMTs) was developed. This paper discusses these new drugs and their possible biological effects in periodontal disease.