Dentistry & Oral Care

Biography

Biography: Ali Kassem

Abstract

Patients with inflammatory or infectious conditions such as periodontitis, peri-implantitis, osteomyelitis, rheumatoid arthritis, septic arthritis or loosened joint prosthesis display varying severity of destruction in the adjacent bone tissue. Bone loss in inflammatory diseases is considered a consequence of cytokine-induced osteoclast formation. Hence, osteotropic cytokines and their receptors have been suggested to be important for the pathogenesis of inflammation-induced osteolysis. Bacterial components recognized by Toll-like receptors (TLRs) in the innate immune system may also be involved. Lipopolysaccharide, fimbria, lipoproteins and flagellin from pathogenic bacteria such as P. gingivalis, S. aureus and S. typhimurium are ligands for TLRs. Since the susceptibility to, or the severity of inflammation-associated bone diseases are likely related to differences in the tissue response and the mechanisms by which pathogens interact with bone cells are not fully understood, we aimed to elucidate the importance of different TLRs for inflammation-induced bone loss. Activation of TLR2 and TLR5 ex vivo and in vivo in periosteal bones increased osteoclast formation, bone resorption and osteoclastic and osteoclastogenic genes expression. We showed that TLR2- and TLR5-induced bone resorption is independent of inflammatory molecules. Interestingly, we found that TLR2 and TLR5 activation in vivo resulted also in locally increased new bone formation at both periosteal and endosteal sides and in the bone marrow compartment. In conclusion, activation of TLR2 and TLR5 in osteoblasts results in bone loss associated with enhanced osteoclast formation and activity, as well as with increased osteoblast differentiation and new bone formation, indicating that inflammation causes bone modelling. The data provide explanation why P. gingivalis and flagella-expressing bacteria can stimulate bone loss. Since TLR2 and TLR5 can also be activated by endogenous ligands produced in inflammatory processes, the data also contribute to the understanding of inflammation-induced bone loss in autoimmune diseases. Keywords: Toll-like receptor, osteoclast, osteoblast, bone resorption, bone formation, P. gingivalis, S. aureus, flagellin.