SLPI is a critical mediator that controls PTH-induced bone formation

Morimoto, Akito; Kikuta, Junichi; Nishikawa, Keizo; Sudo, Takao; Uenaka, Maki; Furuya, Masayuki; Hasegawa, Tetsuo; Hashimoto, Kunihiko; Tsukazaki, Hiroyuki; Seno, Shigeto; Nakamura, Akira; Okuzaki, Daisuke; Sugihara, Fuminori; Ninomiya, Akinori; Yoshimura, Takeshi; Takao-Kawabata, Ryoko; Matsuda, Hideo; Ishii, Masaru

doi:https://doi.org/10.1038/s41467-021-22402-x

SLPI is a critical mediator that controls PTH-induced bone formation

Morimoto, Akito; Kikuta, Junichi; Nishikawa, Keizo et al.

Nature Communications, 2021, 12(1), 2136

Number of Access:3,175（2025-08-14 01:05 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93158

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Title	SLPI is a critical mediator that controls PTH-induced bone formation
Creator	NRID 1000010881740 1000010881740 Scopus Author ID 57200327474 57200327474 CreatorName Morimoto, Akito
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 CreatorName Kikuta, Junichi
	NRID 1000030516290 1000030516290 CreatorName Nishikawa, Keizo
	NRID 1000080631184 1000080631184 researchmap permalink kik kik Scopus Author ID 36497716100 36497716100 CreatorName Sudo, Takao
	NRID 1000090468265 1000090468265 researchmap permalink umaki umaki CreatorName Uenaka, Maki
	NRID 1000020987466 1000020987466 researchmap permalink furuya1019 furuya1019 CreatorName Furuya, Masayuki
	NRID 1000030773048 1000030773048 CreatorName Hasegawa, Tetsuo
	CreatorName Hashimoto, Kunihiko
	CreatorName Tsukazaki, Hiroyuki
	NRID 1000030432462 1000030432462 ORCID 0000-0003-3861-6444 0000-0003-3861-6444 researchmap permalink ssenoo ssenoo Scopus Author ID 57214748425 57214748425 CreatorName Seno, Shigeto
	NRID 1000020344723 1000020344723 CreatorName Nakamura, Akira
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000050381645 1000050381645 researchmap permalink sugiharaf sugiharaf Scopus Author ID 12809512100 12809512100 CreatorName Sugihara, Fuminori
	CreatorName Ninomiya, Akinori
	NRID 1000060402567 1000060402567 researchmap permalink takeshiyoshimura takeshiyoshimura Scopus Author ID 57080284500 57080284500 CreatorName Yoshimura, Takeshi
	CreatorName Takao-Kawabata, Ryoko
	NRID 1000050183950 1000050183950 ORCID 0000-0002-4701-3779 0000-0002-4701-3779 researchmap permalink Hideo_Matsuda Hideo_Matsuda Scopus Author ID 35381793100 35381793100 CreatorName Matsuda, Hideo
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 CreatorName Ishii, Masaru
Description	Morimoto A., Kikuta J., Nishikawa K., et al. SLPI is a critical mediator that controls PTH-induced bone formation. Nature Communications 12, 2136 (2021); https://doi.org/10.1038/s41467-021-22402-x.
Abstract	Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	12(1)
Page	2136
Date of Issued	2021-04-09
Language	English
Handle URL	https://hdl.handle.net/11094/93158
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-021-22402-x
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Communications. 2021, 12(1), p. 2136
DC.title	SLPI is a critical mediator that controls PTH-induced bone formation
DC.creator	Morimoto, Akito
	Kikuta, Junichi
	Nishikawa, Keizo
	Sudo, Takao
	Uenaka, Maki
	Furuya, Masayuki
	Hasegawa, Tetsuo
	Hashimoto, Kunihiko
	Tsukazaki, Hiroyuki
	Seno, Shigeto
	Nakamura, Akira
	Okuzaki, Daisuke
	Sugihara, Fuminori
	Ninomiya, Akinori
	Yoshimura, Takeshi
	Takao-Kawabata, Ryoko
	Matsuda, Hideo
	Ishii, Masaru
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2021-04-09
DC.identifier	https://doi.org/10.1038/s41467-021-22402-x
DC.description	Morimoto A., Kikuta J., Nishikawa K., et al. SLPI is a critical mediator that controls PTH-induced bone formation. Nature Communications 12, 2136 (2021); https://doi.org/10.1038/s41467-021-22402-x.
DCTERMS.abstract	Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93158
citation_title	SLPI is a critical mediator that controls PTH-induced bone formation
citation_author	Morimoto, Akito
	Kikuta, Junichi
	Nishikawa, Keizo
	Sudo, Takao
	Uenaka, Maki
	Furuya, Masayuki
	Hasegawa, Tetsuo
	Hashimoto, Kunihiko
	Tsukazaki, Hiroyuki
	Seno, Shigeto
	Nakamura, Akira
	Okuzaki, Daisuke
	Sugihara, Fuminori
	Ninomiya, Akinori
	Yoshimura, Takeshi
	Takao-Kawabata, Ryoko
	Matsuda, Hideo
	Ishii, Masaru
citation_publisher	Nature Research
citation_language	English
citation_date	2021-04-09
citation_journal_title	Nature Communications
citation_volume	12
citation_issue	1
citation_firstpage	2136
citation_doi	https://doi.org/10.1038/s41467-021-22402-x
citation_public_url	https://hdl.handle.net/11094/93158

SLPI is a critical mediator that controls PTH-induced bone formation

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