Mechanisms of preferential bone formation in myeloma bone lesions by proteasome inhibitors

• Material Type: 博士論文
• Title: Mechanisms of preferential bone formation in myeloma bone lesions by proteasome inhibitors
• Author/Editor: Nakaue, Emiko; Teramachi, Jumpei; Tenshin, Hirofumi; Hiasa, Masahiro; Harada, Takeshi; Oda, Asuka; Inoue, Yusuke; Shimizu, So; Higa, Yoshiki; Sogabe, Kimiko; Oura, Masahiro; Hara, Tomoyo; Sumitani, Ryohei; Maruhashi, Tomoko; Yamagami, Hiroki; Endo, Itsuro; Tanaka, Eiji; Abe, Masahiro
• Author Heading: Nakaue, Emiko; Teramachi, Jumpei; Tenshin, Hirofumi; Hiasa, Masahiro; Harada, Takeshi; Oda, Asuka; Inoue, Yusuke; Shimizu, So; Higa, Yoshiki; Sogabe, Kimiko; Oura, Masahiro; Hara, Tomoyo; Sumitani, Ryohei; Maruhashi, Tomoko; Yamagami, Hiroki; Endo, Itsuro; Tanaka, Eiji; Abe, Masahiro
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2023-04-11; 118 1
• Publication Date (W3CDTF): 2023-04-11
• Alternative Title: 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
• Degree grantor/type: 徳島大学
• Date Granted: 2023-06-08
• Date Granted (W3CDTF): 2023-06-08
• Dissertation Number: 甲第3741号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: Osteoblast; Osteoclast; Proteasome inhibitor; Pulsatile treatment; Multiple myeloma
• Target Audience: 一般
• Note (General): 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.
• Persistent ID (NDL): info:ndljp/pid/13587523; https://dl.ndl.go.jp/pid/13587523
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• Date Accepted (W3CDTF): 2024-05-03T22:07:41+09:00
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/118380
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