Title
Osteoclast precursor differentiation by MCPIP via oxidative stress, endoplasmic reticulum stress, and autophagy
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
ISSN
1674-2788
Recommended Citation
"Osteoclast precursor differentiation by MCPIP via oxidative stress, endoplasmic reticulum stress, and autophagy" (2011). Faculty Bibliography 2010s. 2071.
https://stars.library.ucf.edu/facultybib2010/2071
Comments
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