書誌事項
- タイトル別名
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- Possibility of RANKL as a pharmacological target
抄録
<p>In bone tissue, RANKL acts as a positive regulator of bone turnover through both RANKL forward signaling, which induces osteoclast maturation, and RANKL reverse signaling, which promotes early osteoblast differentiation. Inhibition of osteoclast maturation by blocking RANKL forward signaling inevitably reduces the supply of osteoclast-derived coupling factors, leading to the suppression of bone formation. If we can design an agent that blocks RANKL forward signaling while simultaneously activating RANKL reverse signaling, the influence of reduced supply of osteoclast-derived coupling factors can be mitigated, which may be useful in the treatment of bone destructive diseases. Our previous study has shown that the cross-linking of RANKL molecules on the cell surface triggers the activation reverse signaling. Therefore, we screened various structures of IgG Fc-fusion protein constructs with multivalent binding sites for RANKL by arranging anti-RANKL single-chain antibody variable regions (scFv). Consequently, it was found that a structure in which the domain order inside the scFv was VH-VL order was advantageous for its ability to activate RANKL reverse signaling. Finally, the optimal structure was selected, and its pharmacological activity was evaluated using the ovariectomized mouse model. Results confirmed that the activation of RANKL reverse signaling could mitigate the decrease in bone formation associated with the suppression of osteoclast maturation.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 95 (0), 1-S05-4-, 2022
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390010292711862400
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- ISSN
- 24354953
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
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- 抄録ライセンスフラグ
- 使用不可