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Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo

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Abstract

The release of tumor necrosis factor (TNF)-α from macrophages upon stimulation of lipopolysaccharide (LPS) is a major etiological factor of inflammatory bone disease and elicits the effects through TNF receptors type 1 and 2. Given the importance of TNF-α action on osteoclastic bone resorption, the role of TNF type 2 receptor (TNFR2) on bone resorption has not been elucidated well so far. The purpose of this study is to investigate the role of TNFR2 on LPS-induced inflammatory bone resorption in vivo. LPS at 10 mg/kg (Re 595) was injected subcutaneously on calvariae of wild-type (WT), TNF type 1 receptor (TNFR1)-deficient (KO), and TNFR2 KO mice, killed on day 5 after the LPS injection. The calvarial bone mineral density (BMD) was significantly decreased by LPS compared to the vehicle-injected control in WT mice, but not in TNFR1 KO mice. Interestingly, the decrease of calvarial BMD and the increase of the osteoclast number by LPS in TNFR2 KO mice seemed to be more than those in WT mice. Furthermore, the significant decrease by LPS on the BMD of tibiae, femurs, and lumber vertebrae were observed only in TNFR2 KO mice. Histomorphometric analysis of tibiae showed the significant increases of osteoclast number and surface in the LPS-injected TNFR2 KO mice, and the levels of urinary deoxypyridinoline reflected these increases of bone resorption parameters. The present data indicate that TNFR1 is critical for bone resorption at the site of LPS injection and that TNFR2 might have a protective role on the LPS-induced inflammatory bone resorption process.

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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

    Anower Hussain Mian, Hiroaki Saito, Neil Alles, Hitoyata Shimokawa, Kazuhiro Aoki & Keiichi Ohya

  2. Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan

    Anower Hussain Mian & Neil Alles

Authors
  1. Anower Hussain Mian
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  2. Hiroaki Saito
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  3. Neil Alles
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  4. Hitoyata Shimokawa
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  5. Kazuhiro Aoki
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  6. Keiichi Ohya
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Correspondence to Kazuhiro Aoki.

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Electronic supplementary material The online version of this article (doi: 10.1007/s00774-007-0834-0) contains supplementary material, which is available to authorized users.

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Hussain Mian, A., Saito, H., Alles, N. et al. Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo. J Bone Miner Metab 26, 469–477 (2008). https://doi.org/10.1007/s00774-007-0834-0

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  • DOI: https://doi.org/10.1007/s00774-007-0834-0

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