Research Article
Saturated fatty acids enhance osteoclast survival

https://doi.org/10.1194/jlr.M800626-JLR200Get rights and content
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Hyperlipidemia and marrow fat are associated with lowering bone density in vivo, suggesting that lipid contributes to bone loss. Using bone marrow–derived macrophages, we investigated the effect of saturated fatty acids (SFA) on osteoclastogenesis. The level of free fatty acids and adiposity in bone marrow was significantly elevated in obese mice. SFA increased osteoclast (OC) survival by preventing apoptosis. SFA caused the production of MIP-1α and led to activation of nuclear factor (NF)-κB in the OC. The absence of Toll-like receptor 4 (TLR4) or myeloid differentiation factor 88 (MyD88) abolished the survival effect of SFA on OC.

osteoclast survival
saturated fatty acid
MIP-1α
Toll-like receptor 4
myeloid differentiation factor 88

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This work was supported by Korea (KRF) Grants KRF-2008-314-C00249 and KRF-2009-0066232; by KOSEF Grant R01200700021 08202007; and by Grant A090080 from the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare, and Family Affairs, Republic of Korea.

Abbreviations:

    BMD

    bone mineral density

    BMM

    bone marrow-derived macrophage

    D

    day

    EPA

    17-eicosapentaenoic acid

    FFA

    free fatty acid

    KO

    knockout

    LPS

    lipopolysaccharide

    M-CSF

    macrophage-colony stimulating factor

    MNC

    multinucleated cell

    MyD88

    myeloid differentiation factor 88

    NF

    nuclear factor

    OC

    osteoclast

    RANKL

    receptor activator of nuclear factor-κB ligand

    SFA

    saturated fatty acid

    TLR4

    Toll-like receptor 4

    TNF

    tumor necrosis factor

    TRAP

    tartrate-resistant acid phosphatase

1

S-R. Oh and O-J. Sul contributed equally to this work.