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Inhibition of p38 Mitogen-Activated Protein Kinase Down-regulates the Inflammatory Osteolysis Response to Titanium Particles in a Murine Osteolysis Model

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Abstract

The p38 mitogen-activated protein kinase (p38 MAPK) pathway is involved in the osteoclast differentiation. The aim of the study was to investigate whether SB203580, a p38 MAPK inhibitor, inhibits wear-debris-induced inflammatory osteolysis in mice. Forty-five mice were implanted with calvaria bone from syngeneic littermates; then, titanium (Ti) particles were injected into established air pouches to provoke inflammatory osteolysis. At 14 days after bone/Ti implantation, pouch membranes with intact bone implants underwent histological and molecular analysis. SB203580 had less effect on MMP-9 and TNF-α expression under wear-debris-induced conditions. SB203580, by inhibiting the expression of p38 MAPK and phospho-p38 MAPK, inhibited Ti particle wear-debris-induced inflammatory osteolysis. It also remarkably decreased the number of tartrate-resistant acid phosphatase positive cells in Ti-particle-induced pouch tissues. Results suggest that p38 MAPK may be critical in a murine osteolysis model. SB203580 may notably inhibit wear-debris-induced inflammatory osteolysis by down-regulating expression of MMP-9 and TNF-α via the p38 MAPK pathway.

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ACKNOWLEDGEMENTS

This work was supported by the Interdisciplinary (Engineering–Medical) Research Fund of Shanghai Jiao Tong University (No. YG2011MS30), the Shanghai Municipal Health Bureau Science Fund for Young Scholars (No. 2010QJ036A), and the National Natural Science Foundation of China (No. 81171688).

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Authors and Affiliations

  1. Department of Orthopaedics, The Sixth Affiliated People’s Hospital, School of Medicine, Shanghai Jiao Tong University, No. 600 Yishan Road, Shanghai, 200233, China

    Desheng Chen, Yongyuan Guo, Xin Mao & Xianlong Zhang

  2. Department of Orthopaedics, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China

    Desheng Chen

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  1. Desheng Chen
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  2. Yongyuan Guo
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  3. Xin Mao
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Correspondence to Xianlong Zhang.

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Chen, D., Guo, Y., Mao, X. et al. Inhibition of p38 Mitogen-Activated Protein Kinase Down-regulates the Inflammatory Osteolysis Response to Titanium Particles in a Murine Osteolysis Model. Inflammation 35, 1798–1806 (2012). https://doi.org/10.1007/s10753-012-9500-3

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  • DOI: https://doi.org/10.1007/s10753-012-9500-3

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