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Mouse anti-RANKL antibody delays oral wound healing and increases TRAP-positive mononuclear cells in bone marrow


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タイトル: Mouse anti-RANKL antibody delays oral wound healing and increases TRAP-positive mononuclear cells in bone marrow
著者: Kuroshima, Shinichiro / Al-Salihi, Zeina / Yamashita, Junro
発行日: 2016年 5月
出版者: Springer Berlin Heidelberg / Clinical Oral Investigations, 20(4), pp.727-736; 2016
引用: Clinical Oral Investigations, 20(4): 727-736
抄録: Objectives: Denosumab, a human monoclonal antibody (mAb) that neutralizes receptor activator for nuclear factor κB ligand (RANKL), is associated with osteonecrosis of the jaw. However, the effect of denosumab on oral wounds is unclear. The aim was to determine the effect of anti-RANKL mAb on oral wounds and bone marrow. Materials and methods: The direct effect of the mAb on fibroblasts, macrophages, and osteoclasts were assessed in vitro. In vivo, mouse anti-RANKL mAb was administered to mice for 9 weeks prior to palatal bone denudation surgery. Mice were euthanized 3 weeks post-surgery, and wound healing was histomorphometrically analyzed. Long bones were assessed using micro-computed tomography, quantitative real-time polymerase chain reaction, and flow cytometry. Results: The mAb had no effect on macrophages and fibroblasts but significantly suppressed osteoclast proliferation in vitro. The mAb treatment significantly increased bone mass by suppressing osteoclasts in vivo. The expression of pro-osteoclastic genes was promoted in the bone marrow of the mAb-administered animals. Consistently, the mAb significantly induced the development of tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells (MNCs) but not osteoclasts in bone marrow. The mAb treatment had no effect on gross healing of the palatal wounds. However, significant inflammation was retained in the connective tissue facing the once denuded bone surface. Conclusions: Repair of the damaged palate was delayed, and significant inflammation was sustained in the connective tissue by anti-RANKL mAb treatment. Clinical relevance: Denosumab impairs osteoclastic bone repair. Care should be exercised to minimize osseous trauma when invasive procedures are performed on patients taking denosumab.
キーワード: Antiresorptives / Mouse anti-RANKL monoclonal antibody / Wound healing / Inflammation / TRAP-positive mononuclear cells
URI: http://hdl.handle.net/10069/37948
ISSN: 14326981
DOI: 10.1007/s00784-015-1550-0
権利: © The Author(s) 2015. This article is published with open access at Springerlink.com
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/37948

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