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Osteoclast precursor differentiation by MCPIP via oxidative stress,endoplasmic reticulum stress,and autophagy 被引量:8

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摘要 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 p47PHOX 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.
出处 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 北大核心 2011年第6期360-368,共9页 分子细胞生物学报(英文版)
基金 supported in part by National Institutes of Health Grant HL-69458.
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