Osteoclast precursor differentiation by MCPIP via oxidative stress, endoplasmic reticulum stress, and autophagy

    Authors

    K. K. Wang; J. L. Niu; H. Kim;P. E. Kolattukudy

    Comments

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    Abbreviated Journal Title

    J. Mol. Cell Biol.

    Keywords

    MCP-1; MCPIP; osteoclast differentiation; reactive oxygen species; ER; stress; NF-KAPPA-B; ZINC-FINGER PROTEIN; CERIUM OXIDE NANOPARTICLES; OXYGEN; SPECIES PRODUCTION; RECEPTOR ACTIVATOR; RHEUMATOID-ARTHRITIS; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; BONE-RESORPTION; CELLS; Cell Biology

    Abstract

    Osteoclasts (OCs) are responsible for bone resorption in inflammatory joint diseases. Monocyte chemotactic protein-1 (MCP-1) has been shown to induce differentiation of monocytes to OC precursors, but nothing is known about the underlying mechanisms. Here, we elucidate how MCPIP, induced by MCP-1, mediates this differentiation. Knockdown of MCPIP abolished MCP-1-mediated expression of OC markers, tartrate-resistant acid phosphatase, and serine protease cathepsin K. Expression of MCPIP induced p47(PHOX) and its membrane translocation, reactive oxygen species formation, and induction of endoplasmic reticulum (ER) stress chaperones, up-regulation of autophagy marker, Beclin-1, and lipidation of LC3, and induction of OC markers. Inhibition of oxidative stress attenuated ER stress and autophagy, and suppressed expression of OC markers. Inhibition of ER stress by a specific inhibitor or by knockdown of IRE1 blocked autophagy and induction of OC markers. ER stress inducers, tunicamycin and thapsigargin, induced expression of OC markers. Autophagy inhibition by 3'-methyladenine, LY294002, wortmannin or by knockdown of Beclin-1 or Atg 7 inhibited MCPIP-induced expression of OC markers. These results strongly suggest that MCP-1-induced differentiation of OC precursor cells is mediated via MCPIP-induced oxidative stress that causes ER stress leading to autophagy, revealing a novel mechanistic insight into the role of MCP-1 in OCs differentiation.

    Journal Title

    Journal of Molecular Cell Biology

    Volume

    3

    Issue/Number

    6

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    360

    Last Page

    368

    WOS Identifier

    WOS:000297866600009

    ISSN

    1674-2788

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