Inflammatory Effects of Nitrogen-Containing Bisphosphonates (N-BPs): Modulation by Non-N-BPs
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- Shima Kazuhiro
- Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University Division of Molecular Regulation, Tohoku University Graduate School of Dentistry
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- Tsuchiya Masahiro
- Tohoku Fukushi University
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- Oizumi Takefumi
- Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Tohoku University
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- Takano-Yamamoto Teruko
- Division of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University
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- Sugawara Shunji
- Division of Molecular Regulation, Tohoku University Graduate School of Dentistry
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- Endo Yasuo
- Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Tohoku University
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<p>Bisphosphonates (BPs) are used against diseases with enhanced bone resorption. Those classed as nitrogen-containing BPs (N-BPs) exhibit much stronger anti-bone-resorptive effects than non-nitrogen-containing BPs (non-N-BPs). However, N-BPs carry the risk of inflammatory/necrotic side effects. Depending on their side-chains, BPs are divided structurally into cyclic and non-cyclic types. We previously found in mice that etidronate and clodronate (both non-cyclic non-N-BPs) could reduce the inflammatory effects of all three N-BPs tested (cyclic and non-cyclic types), possibly by inhibiting their entry into soft-tissue cells via SLC20 and/or SLC34 phosphate transporters. Tiludronate is the only available cyclic non-N-BP, but its effects on N-BPs’ side effects have not been examined. Here, we compared the effects of etidronate, clodronate, and tiludronate on the inflammatory effects of six N-BPs used in Japan [three cyclic (risedronate, zoledronate, minodronate) and three non-cyclic (pamidronate, alendronate, ibandronate)]. Inflammatory effects were evaluated in mice by measuring the hind-paw-pad swelling induced by subcutaneous injection of an N-BP (either alone or mixed with a non-N-BP) into the hind-paw-pad. All of six N-BPs tested induced inflammation. Etidronate, clodronate, and the SLC20/34 inhibitor phosphonoformate inhibited this inflammation. Tiludronate inhibited the inflammatory effects of all N-BPs except ibandronate and minodronate, which have higher molecular weights than the other N-BPs. The mRNAs of SLC20a1, SLC20a2, and SLC34a2 (but not of SLC34a1 and SLC34a3) were detected in the soft-tissues of hind-paw-pads. These results suggest that etidronate, clodronate, and phosphonoformate may act non-selectively on phosphate transporter members, while tiludronate may not act on those transporting N-BPs of higher molecular weights.</p>
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 40 (1), 25-33, 2017
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632817664
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- NII論文ID
- 130005188786
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 027818740
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- PubMed
- 28049945
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 使用不可