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Inhibitory effects of triptolide on titanium particle-induced osteolysis and receptor activator of nuclear factor-κB ligand-mediated osteoclast differentiation

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Abstract

Purpose

We examined the effects of triptolide on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and on titanium (Ti) particle-induced osteolysis.

Methods

To examine the effect of triptolide on osteoclast differentiation, bone marrow macrophages (BMMs) were treated with 100 ng/mL of RANKL and 30 ng/mL of macrophage-colony stimulating factor, or co-cultured with osteoblasts stimulated with 10 nM vitamin D3 and 1 μM prostaglandin E2 in the presence or absence of triptolide (2.8–14 nM). Osteoclast differentiation and activation were assessed using tartrate-resistant acid phosphatase staining, reverse transcriptase-polymerase chain reaction analysis to determine differentiation marker gene expression and pit formation assays. To examine the effect of triptolide on wear debris-induced osteolysis, titanium (Ti) particles were injected into the calvaria of ICR mice. Then, the mice were divided into three groups and were orally administered vehicle, or 16 or 32 μg/kg/day triptolide for ten days, followed by histomorphometric analysis.

Results

Triptolide suppressed RANKL-mediated osteoclast differentiation of BMMs in a dose-dependent manner. In a co-culture system, osteoblasts treated with triptolide could not induce osteoclast differentiation of BMMs, which was accompanied by down-regulation of RANKL and up-regulation of osteoprotegrin. Moreover, triptolide significantly inhibited bone resorption, and expression of the bone resorption marker genes. RANKL-induced activation of p38, ERK, and JNK was substantially inhibited by triptolide. Further, in a Ti-induced mouse calvarial erosion model, mice perorally administrated with triptolide showed significant attenuation of Ti-mediated osteolysis.

Conclusion

Our data indicated that triptolide had an anti-osteoclastic effect and significantly suppressed wear debris-induced osteolysis in mice.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MISP) (2008-0062282), and Kyungpook National University Research Fund, 2013.

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Authors and Affiliations

  1. Department of Oral Pathology, IHBR, School of Dentistry, Kyungpook National University, 2177 Dalgubeol daero, Jung gu, Daegu, 700-412, South Korea

    Ju Ang Kim, Jiwon Lim, Hong-In Shin & Eui Kyun Park

  2. Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea

    Hye Jung Ihn & Sang Hyun Kim

  3. Skeletal Diseases Genome Research Centre, Kyungpook National University Hospital, Daegu, South Korea

    Ju-Young Park, Jung Min Hong & Shin-Yoon Kim

  4. Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, South Korea

    Shin-Yoon Kim

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  1. Ju Ang Kim
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Correspondence to Eui Kyun Park.

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Ju Ang Kim and Hye Jung Ihn contributed equally to this work.

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Supplementary Fig. 6

Cell viability of mouse BMM cells with triptolide. The effect of triptolide on BMM cells viability was determined using the MTT cytotoxicity assay. BMM cells were cultured in α-MEM containing 30 ng/mL M-CSF with or without 2.8, 7, or 14 nM of triptolide. (GIF 19 kb)

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Kim, J.A., Ihn, H.J., Park, JY. et al. Inhibitory effects of triptolide on titanium particle-induced osteolysis and receptor activator of nuclear factor-κB ligand-mediated osteoclast differentiation. International Orthopaedics (SICOT) 39, 173–182 (2015). https://doi.org/10.1007/s00264-014-2596-3

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