Lipoproteins are an important bacterial component responsible for bone destruction through the induction of osteoclast differentiation and activation

Authors

  • Jiseon Kim,

    1. Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
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  • Jihyun Yang,

    1. Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
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  • Ok-Jin Park,

    1. Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
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  • Seok-Seong Kang,

    1. Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
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  • Woo-Shin Kim,

    1. Department of Cell and Developmental Biology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
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  • Kenji Kurokawa,

    1. Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Busan, Republic of Korea
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  • Cheol-Heui Yun,

    1. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
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  • Hong-Hee Kim,

    1. Department of Cell and Developmental Biology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
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  • Bok Luel Lee,

    1. Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Busan, Republic of Korea
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  • Seung Hyun Han

    Corresponding author
    1. Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea
    • Address correspondence to: Seung Hyun Han, PhD, Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea. E-mail: shhan-mi@snu.ac.kr

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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. © 2013 American Society for Bone and Mineral Research.

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