Host-response therapeutics for periodontal diseases.
Periodontal diseases are initiated by Gram-negative tooth-associated microbial biofilms that elicit a host response, with resultant osseous and soft tissue destruction. In response to endotoxins derived from periodontal pathogens, several osteoclast-related mediators target the destruction of alveolar bone and supporting connective tissues. Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins, and other osteoclast-derived enzymes. This article focuses on the downstream factors of the osteoclast responsible for the degradation of bone and soft tissues around teeth and oral implants. Furthermore, therapeutic approaches that target MMP-2, -8, and -9 inhibition, such as MMP inhibitors, chemically modified tetracyclines, and subantimicrobial formulations of tetracycline analogues, are discussed. The use of rapid, chair-side tests of MMP activity, in particular for MMP-8 and bone collagen fragments, show strong potential as non-invasive measures of tissue health or disease. In addition, studies using other agents for the preservation of bone mass, such as bisphosphonates that inhibit osteoclast recruitment, are highlighted. The application of these bone-preservation strategies to periodontal management and treatment are discussed in the context of high-risk patients susceptible to disease reactivation or disease complications.
Giannobile
William V
WV
Department of Periodontics and Oral Medicine, Michigan Center for Oral Health Research, University of Michigan School of Dentistry, 24 Frank lloyd Wright Drive, Ann Arbor, MI 48106, USA. wgiannob@umich.edu
D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002403:Cathepsins / Q000037:antagonists & inhibitors; D004164:Diphosphonates / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010510:Periodontal Diseases / Q000188:drug therapy* / Q000382:microbiology; D013754:Tetracyclines / Q000627:therapeutic use; D019714:Tissue Inhibitor of Metalloproteinases / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D013754:Tetracyclines; D019714:Tissue Inhibitor of Metalloproteinases; D002403:Cathepsins