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The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae

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Abstract

Tumor necrosis factor (TNF)-α exerts its biological function via TNF type 1 and type 2 receptors (TNFR1 and TNFR2). We have previously reported that bone resorption induced by lipopolysaccharide (LPS) in TNFR2-deficient mice is accelerated compared to that in wild-type (WT) mice. Although these results suggested that TNFR2 might have a protective role in bone resorption, we could not exclude the possibility that TNFR2 has no role in bone resorption. To clarify the role of TNFR2, we developed a TNF-α-induced bone resorption model using cholesterol-bearing pullulan nanogel as a TNF-α carrier to minimize the influence of inflammatory cytokines other than TNF-α. Injections of human TNF-α (hTNF), an agonist of mouse TNFR1, stimulated bone resorption lacunae on the calvariae in WT mice, but mouse TNF-α (mTNF), an agonist of both mouse TNFR1 and TNFR2, could not. To eliminate the possibility that the TNFR1 agonistic effects of hTNF were stronger than those of mTNF, we used the same model in TNFR2-deficient mice. Injection of mTNF resulted in clear bone resorption lacunae to the same extent observed after using hTNF in the TNFR2-deficient mice. Histomorphometric analysis of osteoclast number supported the observed changes in bone resorption lacunae. These data suggest that TNFR2 has a protective role in TNF-α-induced bone resorption.

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Acknowledgments

We thank Prof. A. Yamaguchi and Prof. K. Moriyama (Tokyo Medical and Dental University) for their helpful suggestions. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, to K. O. (19390471) and K. A. (17659584 and 19390472).

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All authors have no conflict of interest.

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Authors and Affiliations

  1. Section of Pharmacology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Kenichi Nagano, Neil Alles, Yukihiko Tamura, Keiichi Ohya & Kazuhiro Aoki

  2. The Japan Society for the Promotion of Science Postdoctoral Fellowship for Foreign Researchers, Tokyo, 102-0083, Japan

    Neil Alles

  3. Department of General and Dental Pharmacology, City Dental College and Hospital, Dhaka, 1219, Bangladesh

    Anower Hussain Mian

  4. Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, 101-0062, Japan

    Asako Shimoda & Kazunari Akiyoshi

  5. Global Center of Excellence Program for International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan

    Asako Shimoda & Kazunari Akiyoshi

  6. Department of Materials Processing, Graduate School of Engineering, Tohoku University, Sendai, Miyagi, 980-8579, Japan

    Nobuyuki Morimoto

  7. Department of Pedodontics, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan

    Hitoyata Shimokawa

  8. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan

    Kazunari Akiyoshi

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  1. Kenichi Nagano
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Correspondence to Kazuhiro Aoki.

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Nagano, K., Alles, N., Mian, A.H. et al. The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae. J Bone Miner Metab 29, 671–681 (2011). https://doi.org/10.1007/s00774-011-0270-z

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