title: Lipoproteins are an important bacterial component responsible for bone destruction through the induction of osteoclast differentiation and activation.
abstract: Bacterial infection can cause inflammatory bone diseases accompanied by the bone destruction resulting from excess generation of osteoclasts. Although lipoproteins are one of the major immunostimulating components of bacteria, little is known about their effects on bone metabolism. In this study, we investigated the role of lipoproteins in bacteria-induced bone destruction using Staphylococcus aureus wild type, its lipoprotein-deficient mutant, and synthetic lipopeptides Pam2CSK4 and Pam3CSK4 known to mimic bacterial lipoproteins. Formaldehyde-inactivated S. aureus or the synthetic lipopeptides induced severe bone loss in the femurs of mice after intraperitoneal administration and in a calvarial bone implantation model, whereas the lipoprotein-deficient S. aureus did not show such effects. Mechanism studies further identified three action mechanisms for the lipopeptide-induced osteoclast differentiation and bone resorption via (i) enhancement of osteoclast differentiation through Toll-like receptor 2 and MyD88-dependent signaling pathways; (ii) induction of pro-inflammatory cytokines, TNF-α and IL-6; and (iii) upregulation of RANKL expression with downregulation of osteoprotegerin expression in osteoblasts. Taken together, these results suggest that lipoprotein might be an important bacterial component responsible for bone destruction during bacterial infections through augmentation of osteoclast differentiation and activation.
authors: Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors: Jiseon
authors: J
authors: Kim
authors: Jihyun
authors: J
authors: Yang
authors: Ok-Jin
authors: OJ
authors: Park
authors: Seok-Seong
authors: SS
authors: Kang
authors: Woo-Shin
authors: WS
authors: Kim
authors: Kenji
authors: K
authors: Kurokawa
authors: Cheol-Heui
authors: CH
authors: Yun
authors: Hong-Hee
authors: HH
authors: Kim
authors: Bok Luel
authors: BL
authors: Lee
authors: Seung Hyun
authors: SH
authors: Han
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000235:genetics / Q000382:microbiology* / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D055666:Lipopeptides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053244:Osteoprotegerin / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D053245:RANK Ligand / Q000378:metabolism; D011859:Radiography; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D013211:Staphylococcus aureus / Q000737:chemistry*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015850:Interleukin-6; D055666:Lipopeptides; D008074:Lipoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053244:Osteoprotegerin; C508075:Pam(3)CSK(4) peptide; C560312:Pam2CSK4 lipopeptide; D053245:RANK Ligand; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D004247:DNA
keywords: BACTERIAL LIPOPROTEIN; BONE RESORPTION; LIPOPEPTIDE; OSTEOCLAST DIFFERENTIATION; TLR2