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Inhibition of osteolysis after local administration of osthole in a TCP particles-induced osteolysis model

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Abstract

Purpose

Wear debris-induced osteolysis and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. However, no effective measures for the prevention and treatment of particles-induced osteolysis currently exist. Here, we investigated the efficacy of local administration of osthole on tricalcium phosphate (TCP) particles-induced osteolysis in a murine calvarial model.

Methods

TCP particles were implanted over the calvaria of ICR mice, and established TCP particles-induced osteolysis model. On days one, four, seven, ten and thirteen post-surgery, osthole (10 mg/kg) or phosphate buffer saline (PBS) were subcutaneously injected into the calvaria of TCP particles-implanted or sham-operated mice. Two weeks later, blood, the periosteum and the calvaria were collected and processed for bone turnover markers, pro-inflammatory cytokine, histomorphometric and molecular analysis.

Results

Osthole (10 mg/kg) markedly prevented TCP particles-induced osteoclastogenesis and bone resorption in a mouse calvarial model. Osthole also inhibited the decrease of serum osteocalcin level and calvarial alkaline phosphatase (ALP) activity, and prevented the increase in the activity of tartrate resistant acid phosphatase (TRAP) and cathepsin K in the mouse calvaria. Furthermore, osthole obviously reduced the release of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) into the periosteum. Western blotting demonstrated TCP particles caused a remarkable endoplasmic reticulum (ER) stress response in the mouse calvaria, which was obviously blocked by osthole treatment.

Conclusion

These results suggest that local administration of osthole inhibits TCP particles-induced osteolysis in the mouse calvarial in vivo, which may be mediated by inhibition of the ER stress signaling pathway, and it will be developed as a new drug in the prevention and treatment of destructive diseases caused by prosthetic wear particles.

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Acknowledgments

This work was supported by Zhejiang Provincial Natural Science Foundation of China (No. LY13H060003 and No. LY15H180012), Scientific Research Foundation of Traditional Chinese Medicine in Zhejiang Province (No.2012ZB161) and Science & Technology Innovation Project of College Students in Zhejiang Province (No. 2013R426025).

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Authors and Affiliations

  1. College of Medicine, Shaoxing University, Huancheng West Road 508, 312000, Shaoxing, China

    Shumin Lv, Yun Zhang, Hongjiao Mao, Cailing Pan, Mingxiao Gan, Jiawen Fan & Guoxia Wang

  2. College of Life Information Science & Instrument Engineering, Hangzhou Dianzi University, Xiasha Higher Education Zone, Hangzhou, 310018, China

    Ming Yan

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  1. Shumin Lv
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  2. Yun Zhang
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  3. Ming Yan
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Correspondence to Yun Zhang.

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Lv, S., Zhang, Y., Yan, M. et al. Inhibition of osteolysis after local administration of osthole in a TCP particles-induced osteolysis model. International Orthopaedics (SICOT) 40, 1545–1552 (2016). https://doi.org/10.1007/s00264-015-3021-2

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  • DOI: https://doi.org/10.1007/s00264-015-3021-2

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