Lipopolysaccharide-Induced Osteoclastogenesis in Src Homology 2-Domain Phosphatase-1-Deficient Viable Motheaten Mice

摘要: Osteoclasts are hemopoietic cells that participate in bone resorption and remodeling. Receptor activator of nuclear factor-kappaB ligand (RANKL) macrophage colony-stimulating factor (M-CSF) critical for development osteoclasts. The Toll-like receptor (TLR) family shares some the downstream signaling with RANK. TLR4 ligand, lipopolysaccharide (LPS), is reported to accelerate lysis; however, via TLRs has never been induce osteoclastogenesis without RANKL. In this study we showed significant numbers mature osteoclasts were generated from protein tyrosine phosphatase Src homology 2-domain phosphatase-1-defective Hcph(me-v)/Hcph(me-v) (me(v)/me(v)) marrow presence M-CSF LPS addition RANKL culture. This plus LPS-induced was not inhibited by an anti-TNFalpha antagonistic antibody or osteoprotegerin, a decoy replacement TLR ligands only occurred LPS. Other ligands, peptidoglycan TLR2 unmethylated CpG oligonucleotide TLR9, did support osteoclast generation. precursors as well RANKL-responsive present Kit-positive cell-enriched fraction cells. Although me(v)/me(v) required comparable concentration TNFalpha wild-type initiation osteoclastogenesis, multinucleated cultures significantly increased equivalent dose M-CSF. These results indicate defect phosphatase-1 function accelerates physiological RANKL/RANK, but also acquires novel pathway