Secretory clusterin inhibits osteoclastogenesis by attenuating M-CSF-dependent osteoclast precursor cell proliferation

Bongkun Choi, Soon Suk Kang, Sang Wook Kang, Bon Hong Min, Eun Jin Lee, Da Hyun Song, Sang Min Kim, Youngsup Song, Seung Yong Yoon, Eun Ju Chang

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)


    Secretory clusterin (sCLU)/apolipoprotein J is a multifunctional glycoprotein that is ubiquitously expressed in various tissues. Reduced sCLU in the joints of patients with bone erosive disease is associated with disease activity; however, its exact role has yet to be elucidated. Here, we report that CLU is expressed and secreted during osteoclastogenesis in mouse bone marrow-derived macrophages (BMMs) that are treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). CLU-deficient BMMs obtained from CLU-/- mice exhibited no significant alterations in OC differentiation in comparison with BMMs obtained from wild-type mice. In contrast, exogenous sCLU treatment significantly inhibited OC formation in both BMMs and OC precursor cultures. The inhibitory effect of sCLU was more prominent in BMMs than OC precursor cultures. Interestingly, treating BMMs with sCLU decreased the proliferative effects elicited by M-CSF and suppressed M-CSF-induced ERK activation of OC precursor cells without causing apoptotic cell death. This study provides the first evidence that sCLU reduces OC formation by inhibiting the actions of M-CSF, thereby suggesting its protective role in bone erosion.

    Original languageEnglish
    Pages (from-to)105-109
    Number of pages5
    JournalBiochemical and biophysical research communications
    Issue number1
    Publication statusPublished - 2014 Jul 18

    Bibliographical note

    Funding Information:
    We thank YS Cho and HS Kwon (Department of Internal Medicine, Asan Medical Center) for providing the CLU −/− mice. This project was supported by a National Research Foundation of Korea (NRF) MRC grant funded by the Korea Government (MSIP) ( 2008-0062286 ).


    • Clusterin
    • Differentiation
    • ERK
    • Osteoclast
    • Proliferation

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology


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