Lipopolysaccharide (LPS) is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and\nimmunological activity. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological\nactivity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies\nhave shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP.\nMDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP\ninduces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP\nenhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-�ºB ligand\n(RANKL) expression and toll-like receptor 4 (TLR4) expression both in vivo and in vitro. Additionally, MDP enhances LPSinduced\nmitogen-activated protein kinase (MAPK) signaling in stromal cells. Taken together, these findings suggest that MDP\nplays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological\nactivities, primarily in relation to osteoclastogenesis.
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