[Bone destruction caused by osteoclasts].
Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) are components of bacterial 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/interleukin (IL)-1R signaling and activates MAP/ERK kinase (MEK)/ERK pathway to induce receptor activator of NF-kappaB ligand (RANKL) expression in osteoblasts. Osteoblasts express nucleotide oligomerization domain (NOD)2, an intracellular sensor for MDP, in response to LPS, IL-1 and TNF. NOD2 binds receptor-interacting protein (RIP2), a serine/threonine kinase which transduces NF-kappaB signaling. MDP synergistically enhances osteoclast formation induced by LPS, IL-1 and TNF through RANK ligand up-regulation in osteoblasts. TLR4 and NOD2 recognize bacterial components on cell surfaces and inside cells, respectively, and these signals up-regulate RANKL expression in osteoblasts, which results in enhancing osteoclast formation and function.
Yamashita
Teruhito
T
Matsumoto Dental University, Institute for Oral Science.
Takahashi
Naoyuki
N
Yang
Shuhua
S
Sato
Nobuaki
N
Udagawa
Nobuyuki
N
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000502:physiology
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C495345:TLR4 protein, human; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D051197:Toll-Like Receptor 4; D000119:Acetylmuramyl-Alanyl-Isoglutamine