Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss

Bun, Masayuki; Ukon, Yuichiro; Ikuta, Masato; Kitahara, Takayuki; Furuichi, Takuya; Hirai, Hiromasa; Tateiwa, Daisuke; Kanie, Yuya; Furuya, Masayuki; Fujimori, Takahito; Otsuru, Satoru; Okada, Seiji; Kaito, Takashi

doi:https://doi.org/10.1111/acel.70331

Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss

Bun, Masayuki; Ukon, Yuichiro; Ikuta, Masato et al.

Aging Cell, 2025, 25(1), e70331

アクセス数:8件（2026-02-16 07:33 集計）

固定URL: https://hdl.handle.net/11094/103708

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タイトル	Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss
著者	著者名 Bun, Masayuki
	NRID 1000050964334 1000050964334 ORCID 0000-0002-0747-8854 0000-0002-0747-8854 researchmap permalink yuichiro.ukon yuichiro.ukon 著者名 Ukon, Yuichiro
	著者名 Ikuta, Masato
	著者名 Kitahara, Takayuki
	著者名 Furuichi, Takuya
	著者名 Hirai, Hiromasa
	著者名 Tateiwa, Daisuke
	NRID 1000010896377 1000010896377 ORCID 0000-0001-5977-1959 0000-0001-5977-1959 researchmap permalink ykanie1985 ykanie1985 Scopus Author ID 57567389000 57567389000 著者名 Kanie, Yuya
	著者名 Furuya, Masayuki
	NRID 1000080546888 1000080546888 ORCID 0000-0002-2758-7919 0000-0002-2758-7919 researchmap permalink fujimori_takahito fujimori_takahito Scopus Author ID 35271904600 35271904600 著者名 Fujimori, Takahito
	著者名 Otsuru, Satoru
	NRID 1000030448435 1000030448435 ORCID 0000-0002-5107-8209 0000-0002-5107-8209 researchmap permalink okadaseiji okadaseiji Scopus Author ID 35079139100 35079139100 著者名 Okada, Seiji
	NRID 1000070623982 1000070623982 ORCID 0000-0003-4882-2997 0000-0003-4882-2997 researchmap permalink 911_0 911_0 Scopus Author ID 25824322100 25824322100 著者名 Kaito, Takashi
キーワード等	bone loss
	cellular senescence
	osteoblast
	osteoporosis
	parathyroid hormone
内容	Bun M., Ukon Y., Ikuta M., et al. Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss. Aging Cell 25, e70331 (2026); https://doi.org/10.1111/acel.70331.
抄録	Osteoporosis is characterized by reduced bone mass and structural deterioration, leading to increased fracture risk, particularly in older adults. Parathyroid hormone (PTH) is a widely used anabolic therapy for osteoporosis; however, rapid bone loss after treatment discontinuation presents a significant clinical challenge. Cellular senescence has been implicated in age-related bone fragility. However, its role in PTH-induced bone remodeling and post-treatment bone loss remains unclear. This study aimed to investigate the effects of PTH administration frequency on bone microarchitecture and cellular senescence in young and aged mice. High-frequency PTH administration improved trabecular bone volume in both age groups, but caused cortical bone thinning, increased porosity, and elevated osteoclast activity in aged mice. PTH induces senescent osteoblast-lineage-enriched cell accumulation in aged, but not young mice, accompanied by upregulation of senescence-associated markers and activation of the mechanistic Target of Rapamycin Complex 1 pathway. Co-administration of the senolytic agents dasatinib and quercetin during PTH treatment reduced senescent cell burden, improved cortical porosity, and mitigated rapid bone loss after PTH discontinuation in aged mice. These findings indicate that senescent osteoblast-lineage-enriched cells contribute to bone fragility and post-treatment bone loss in aged individuals, suggesting that targeting senescence may enhance the efficacy and sustainability of PTH therapy for osteoporosis.
出版者	John Wiley and Sons Inc
収録物名	Aging Cell
巻(号)	25(1)
ページ	e70331
刊行年月	2025-12-23
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103708
PISSN	14749718
eISSN	14749726
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1111/acel.70331
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
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	Aging Cell. 2025, 25(1), p. e70331
DC.title	Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss
DC.creator	Bun, Masayuki
	Ukon, Yuichiro
	Ikuta, Masato
	Kitahara, Takayuki
	Furuichi, Takuya
	Hirai, Hiromasa
	Tateiwa, Daisuke
	Kanie, Yuya
	Furuya, Masayuki
	Fujimori, Takahito
	Otsuru, Satoru
	Okada, Seiji
	Kaito, Takashi
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-12-23
DC.identifier	https://doi.org/10.1111/acel.70331
DC.subject	bone loss
	cellular senescence
	osteoblast
	osteoporosis
	parathyroid hormone
DC.description	Bun M., Ukon Y., Ikuta M., et al. Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss. Aging Cell 25, e70331 (2026); https://doi.org/10.1111/acel.70331.
DCTERMS.abstract	Osteoporosis is characterized by reduced bone mass and structural deterioration, leading to increased fracture risk, particularly in older adults. Parathyroid hormone (PTH) is a widely used anabolic therapy for osteoporosis; however, rapid bone loss after treatment discontinuation presents a significant clinical challenge. Cellular senescence has been implicated in age-related bone fragility. However, its role in PTH-induced bone remodeling and post-treatment bone loss remains unclear. This study aimed to investigate the effects of PTH administration frequency on bone microarchitecture and cellular senescence in young and aged mice. High-frequency PTH administration improved trabecular bone volume in both age groups, but caused cortical bone thinning, increased porosity, and elevated osteoclast activity in aged mice. PTH induces senescent osteoblast-lineage-enriched cell accumulation in aged, but not young mice, accompanied by upregulation of senescence-associated markers and activation of the mechanistic Target of Rapamycin Complex 1 pathway. Co-administration of the senolytic agents dasatinib and quercetin during PTH treatment reduced senescent cell burden, improved cortical porosity, and mitigated rapid bone loss after PTH discontinuation in aged mice. These findings indicate that senescent osteoblast-lineage-enriched cells contribute to bone fragility and post-treatment bone loss in aged individuals, suggesting that targeting senescence may enhance the efficacy and sustainability of PTH therapy for osteoporosis.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	103708
citation_title	Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss
citation_author	Bun, Masayuki
	Ukon, Yuichiro
	Ikuta, Masato
	Kitahara, Takayuki
	Furuichi, Takuya
	Hirai, Hiromasa
	Tateiwa, Daisuke
	Kanie, Yuya
	Furuya, Masayuki
	Fujimori, Takahito
	Otsuru, Satoru
	Okada, Seiji
	Kaito, Takashi
citation_publisher	John Wiley and Sons Inc
citation_language	英語
citation_date	2025-12-23
citation_journal_title	Aging Cell
citation_volume	25
citation_issue	1
citation_firstpage	e70331
citation_doi	https://doi.org/10.1111/acel.70331
citation_public_url	https://hdl.handle.net/11094/103708

Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1–34 Administration and Bone Loss

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