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ID 118380
タイトル別表記
プロテアソーム阻害薬による骨髄腫骨病変部における優先的な骨形成のメカニズムについて
著者
中上, 絵美子 徳島大学大学院口腔科学研究科(口腔科学専攻)
Oda, Asuka Tokushima University
Inoue, Yusuke Tokushima University
Higa, Yoshiki Tokushima University
Maruhashi, Tomoko Tokushima University
キーワード
Osteoblast
Osteoclast
Proteasome inhibitor
Pulsatile treatment
Multiple myeloma
資料タイプ
学位論文
抄録
Proteasome inhibitors (PIs) can preferentially restore bone in bone-defective lesions of patients with multiple myeloma (MM) who respond favorably to these drugs. Most prior in vitro studies on PIs used continuous exposure to low PI concentrations, although pharmacokinetic analysis in patients has shown that serum concentrations of PIs change in a pulsatile manner. In the present study, we explored the effects of pulsatile treatment with PIs on bone metabolism to simulate in vivo PI pharmacokinetics. Pulsatile treatment with bortezomib, carfilzomib, or ixazomib induced MM cell death but only marginally affected the viability of osteoclasts (OCs) with F-actin ring formation. Pulsatile PI treatment suppressed osteoclastogenesis in OC precursors and bone resorption by mature OCs. OCs robustly enhanced osteoblastogenesis in cocultures with OCs and MC3T3-E1 pre-osteoblastic cells, indicating OC-mediated coupling to osteoblastogenesis. Importantly, pulsatile PI treatment did not impair robust OC-mediated osteoblastogenesis. These results suggest that PIs might sufficiently reduce MM cell-derived osteoblastogenesis inhibitors to permit OC-driven bone formation coupling while suppressing OC differentiation and activity in good responders to PIs. OC-mediated coupling to osteoblastogenesis appears to be a predominant mechanism for preferential occurrence of bone regeneration at sites of osteoclastic bone destruction in good responders.
掲載誌名
International Journal of Hematology
ISSN
09255710
18653774
cat書誌ID
AA10797094
出版者
Springer Nature
118
1
開始ページ
88
終了ページ
98
発行日
2023-04-11
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Emiko Nakaueの学位論文として提出され,学位審査・授与の対象となっている。
This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12185-023-03601-2
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3741号
学位記番号
甲口第497号
学位授与年月日
2023-06-08
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
病院
医学系