lipoteichoic-acid and Osteolysis

The signaling network involved in the pathogenesis of periodontal disease is not yet fully understood. This review aims to describe possible mechanisms through which the bacterial modulators may be linked directly or indirectly to the process of alveolar bone loss in periodontitis. From the late 1970s to present, new paradigm shifts have been developed regarding our understanding of pathological bone remodeling in periodontal disease. Upcoming evidence suggests that in periodontal disease the local immune response is exacerbated and involves the existence of signaling pathways that have been shown to modulate bone-cell function leading to alveolar bone loss. Those complex signaling pathways have been observed not only between bacteria but also between bacteria and the gingival surface of the host. More specifically, it has been shown that bacteria, through their secretion molecules, may interact indirectly and directly with immune-type cells of the host, resulting in the production of osteolytic agents that enhance bone resorption. Further research is required to provide a clear understanding of the role of these molecules in the pathogenesis of periodontal disease, and the availability of new technologies, such as next-generation sequencing and metagenomic analysis, may be useful tools in achieving this.

Topics: Alveolar Bone Loss; Antigens, Bacterial; Autoimmunity; Bacteria; Bacterial Physiological Phenomena; Bone Remodeling; Cytokines; Humans; Lipopeptides; Lipopolysaccharides; Lipoproteins; Osteoclasts; Osteolysis; Periodontal Diseases; Periodontal Pocket; Periodontitis; Teichoic Acids

Device-associated infections after implants or endoprostheses inflict local inflammation and ultimately osteolysis, a clinical entity referred to as posttraumatic osteomyelitis. The underlying molecular mechanisms are not yet known; formation of bacterial biofilms on the implant is presumed, conferring resistance to antibiotics and to host defense mechanisms as well. To gain insight into the pathogenesis of post-traumatic osteomyelitis, the infected site was analyzed for the presence of immunocompetent cells. In 18 patients, the infected site was rinsed intraoperatively. This so-called lavage contained 1-2 x 107 leukocytes, predominantly highly activated polymorphonuclear neutrophils (PMNs), as characterized by low expression of CD62L (selectin), and high expression of the adhesion protein CD18, of the high-affinity immunoglobulin (IgG) receptor CD64, and of the LPS-receptor CD14. CD16, the low-affinity IgG receptor, was affected in some patients only. Because the majority of infections were caused by staphylococci species, the effect of bacteria-derived lipoteichoic acid on PMN of healthy donors was tested in vitro. A similar activation pattern was found: rapid down-regulation of CD62L, a slower loss of CD16, and upregulation of CD18, CD64, and CD14. Lipoteichoic acid signaling required p38 mitogen-activated protein kinase and resulted in induction of CD14-specific mRNA and de novo protein synthesis. We conclude that PMNs infiltrate the infected site, but despite local activation they are unable to clear the bacteria, presumably because of biofilm formation. Our data are consistent with the hypothesis that during the ineffective "frustrated" attempt to phagocytose, PMNs release cytotoxic and proteolytic entities that in turn contribute to the progression of tissue injury and ultimately to osteolysis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; CD18 Antigens; Down-Regulation; Female; Flow Cytometry; Humans; Inflammation; Knee; L-Selectin; Leukocytes; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Mitogen-Activated Protein Kinases; Neutrophils; Osteolysis; Osteomyelitis; p38 Mitogen-Activated Protein Kinases; Radiography; Receptors, IgG; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Shock, Traumatic; Teichoic Acids; Time Factors; Up-Regulation