[Bone destruction caused by osteoclasts]

Abstract

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.