Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model

Mori, Maya; Nishizawa, Chiaki; Usami, Yu; Takahata, Sosuke; Matsushita, Yutaka; Isomura, Emiko Tanaka; Tanaka, Susumu; Kogo, Mikihiko; Aikawa, Tomonao; Miyagawa, Kazuaki

doi:https://doi.org/10.1016/j.ajoms.2025.12.007

Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model

Mori, Maya; Nishizawa, Chiaki; Usami, Yu et al.

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 2025

アクセス数:7件（2026-02-15 23:06 集計）

固定URL: https://hdl.handle.net/11094/103700

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タイトル	Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model
著者	著者名 Mori, Maya
	NRID 1000031020183 1000031020183 著者名 Nishizawa, Chiaki
	NRID 1000080444579 1000080444579 ORCID 0000-0003-4816-2132 0000-0003-4816-2132 researchmap permalink yuusami yuusami Scopus Author ID 55263165500 55263165500 著者名 Usami, Yu
	NRID 1000090964875 1000090964875 著者名 Takahata, Sosuke
	著者名 Matsushita, Yutaka
	NRID 1000070397701 1000070397701 ORCID 0000-0002-7855-9600 0000-0002-7855-9600 researchmap permalink read0076452 read0076452 Scopus Author ID 55667115400 55667115400 著者名 Isomura, Emiko Tanaka
	NRID 1000000367541 1000000367541 ORCID 0000-0002-0306-3627 0000-0002-0306-3627 researchmap permalink mes5 mes5 Scopus Author ID 56395750500 56395750500 著者名 Tanaka, Susumu
	NRID 1000020205371 1000020205371 ORCID 0000-0002-4556-2491 0000-0002-4556-2491 researchmap permalink 4321Kogo2 4321Kogo2 Scopus Author ID 7003762492 7003762492 著者名 Kogo, Mikihiko
	NRID 1000000362674 1000000362674 著者名 Aikawa, Tomonao
	NRID 1000050635381 1000050635381 ORCID 0000-0003-4014-1847 0000-0003-4014-1847 researchmap permalink kaz-miyagawa kaz-miyagawa Scopus Author ID 37012083900 37012083900 著者名 Miyagawa, Kazuaki
キーワード等	anti-RANKL antibody
	Antiresorptive agents
	Bisphosphonate
	Medication-related osteonecrosis of the jaw
	Osteocytes
内容	Mori M., Nishizawa C., Usami Y., et al. Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology (2025); https://doi.org/10.1016/j.ajoms.2025.12.007.
抄録	Objective: To investigate how zoledronic acid (ZOL) and the anti-receptor activator of nuclear factor-κB ligand (RANKL) antibody OYC1 differentially affected osteocyte function relevant to medication-related osteonecrosis of the jaw (MRONJ) pathogenesis in mice. Methods: Nine-week-old ovariectomized (OVX) mice were treated with ZOL (200 µg/kg, intraperitoneally, twice weekly for 4 weeks), OYC1 (5 mg/kg, single subcutaneous dose), or saline control. Tibial bone microarchitecture was assessed by micro-computed tomography, osteocyte and osteoblast morphologies were analyzed histologically, and the gene expression of osteoblast- and osteocyte-related markers was evaluated. Levels of sclerostin, a key osteocyte-derived protein, in the tibial cortical bone were analyzed using immunohistochemistry. Results: Compared with the control (OVX-CTL) group, both the OVX-ZOL and OVX-OYC1 groups showed significantly higher bone volume fraction (p < 0.001) and trabecular thickness (p < 0.001) and number (p < 0.001). Osteoblast activity on the bone surfaces of the proximal tibia was less frequent in both the OVX-ZOL and OVX-OYC1 groups than in the OVX-CTL group. Although the osteocyte number was unchanged, Sost expression was significantly increased in the OVX-OYC1 group and decreased in the OVX-ZOL group. The proportion of sclerostin-positive osteocytes in the tibial cortical bone was higher in the OVX-OYC1 group than in the OVX-CTL group (p = 0.003). Conclusions: Both ZOL and OYC1 restore bone loss but exert distinct effects on osteocytes: ZOL decreases Sost/sclerostin expression, whereas OYC1 increases it. These findings suggest that ZOL and anti-RANKL antibodies differentially modulate osteocyte function, warranting further studies to clarify mechanisms underlying MRONJ development.
出版者	Elsevier Ltd
収録物名	Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
刊行年月	2025-12-09
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103700
PISSN	22125558
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1016/j.ajoms.2025.12.007
アクセス権	embargoed access
権利情報	© 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
権利情報	The full-text file will be made open to the public on 9 December 2026 in accordance with the publisher's policy.
出版タイプ	Accepted Manuscript
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 2025
DC.title	Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model
DC.creator	Mori, Maya
	Nishizawa, Chiaki
	Usami, Yu
	Takahata, Sosuke
	Matsushita, Yutaka
	Isomura, Emiko Tanaka
	Tanaka, Susumu
	Kogo, Mikihiko
	Aikawa, Tomonao
	Miyagawa, Kazuaki
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-12-09
DC.identifier	https://doi.org/10.1016/j.ajoms.2025.12.007
DC.subject	anti-RANKL antibody
	Antiresorptive agents
	Bisphosphonate
	Medication-related osteonecrosis of the jaw
	Osteocytes
DC.description	Mori M., Nishizawa C., Usami Y., et al. Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology (2025); https://doi.org/10.1016/j.ajoms.2025.12.007.
DCTERMS.abstract	Objective: To investigate how zoledronic acid (ZOL) and the anti-receptor activator of nuclear factor-κB ligand (RANKL) antibody OYC1 differentially affected osteocyte function relevant to medication-related osteonecrosis of the jaw (MRONJ) pathogenesis in mice. Methods: Nine-week-old ovariectomized (OVX) mice were treated with ZOL (200 µg/kg, intraperitoneally, twice weekly for 4 weeks), OYC1 (5 mg/kg, single subcutaneous dose), or saline control. Tibial bone microarchitecture was assessed by micro-computed tomography, osteocyte and osteoblast morphologies were analyzed histologically, and the gene expression of osteoblast- and osteocyte-related markers was evaluated. Levels of sclerostin, a key osteocyte-derived protein, in the tibial cortical bone were analyzed using immunohistochemistry. Results: Compared with the control (OVX-CTL) group, both the OVX-ZOL and OVX-OYC1 groups showed significantly higher bone volume fraction (p < 0.001) and trabecular thickness (p < 0.001) and number (p < 0.001). Osteoblast activity on the bone surfaces of the proximal tibia was less frequent in both the OVX-ZOL and OVX-OYC1 groups than in the OVX-CTL group. Although the osteocyte number was unchanged, Sost expression was significantly increased in the OVX-OYC1 group and decreased in the OVX-ZOL group. The proportion of sclerostin-positive osteocytes in the tibial cortical bone was higher in the OVX-OYC1 group than in the OVX-CTL group (p = 0.003). Conclusions: Both ZOL and OYC1 restore bone loss but exert distinct effects on osteocytes: ZOL decreases Sost/sclerostin expression, whereas OYC1 increases it. These findings suggest that ZOL and anti-RANKL antibodies differentially modulate osteocyte function, warranting further studies to clarify mechanisms underlying MRONJ development.
DC.rights	© 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
DC.rights	The full-text file will be made open to the public on 9 December 2026 in accordance with the publisher's policy.
DC.format	103700
citation_title	Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model
citation_author	Mori, Maya
	Nishizawa, Chiaki
	Usami, Yu
	Takahata, Sosuke
	Matsushita, Yutaka
	Isomura, Emiko Tanaka
	Tanaka, Susumu
	Kogo, Mikihiko
	Aikawa, Tomonao
	Miyagawa, Kazuaki
citation_publisher	Elsevier Ltd
citation_language	英語
citation_date	2025-12-09
citation_journal_title	Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
citation_doi	https://doi.org/10.1016/j.ajoms.2025.12.007
citation_public_url	https://hdl.handle.net/11094/103700

Differential sclerostin secretion by zoledronic acid and an Anti-RANKL antibody in the tibia of an ovariectomized mouse model

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