[Osteoclastogenesis through TLR/NOD signaling].
Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) are components of microbial cell walls that cause innate immune responses and inflammation. Toll-like receptor 4 (TLR4) is a receptor for LPS and transduces signals through myeloid differentiation factor 88 (MyD88), which plays essential roles in the TLR/IL-1R signaling and activates NF-kappaB and MAP kinase pathways to induce RANKL expression in osteoblasts. Osteoblasts express NOD2, an intracellular sensor for MDP, in response to LPS, IL-1 and TNF. NOD2 binds RIP2, a serine/threonine kinase which transduces NF-kappaB signaling. Thus MDP synergistically enhances osteoclast formation induced by LPS, IL-1 and TNF through RANK ligand up-regulation in osteoblasts. In summary, innate immune receptors, TLR4 and NOD2, recognize bacterial components on cell surfaces and inside cells, respectively, and these signals cross-talk to induce RANKL expression in osteoblasts, which results in enhancing osteoclast formation and function.
Yamashita
Teruhito
T
Institute for Oral Science, Matsumoto Dental University.
Yang
Shuhua
S
Udagawa
Nobuyuki
N
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011956:Receptors, Cell Surface / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011956:Receptors, Cell Surface; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors