Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice

Takami, Kenji; Okamoto, Kazuki; Etani, Yuki; Hirao, Makoto; Miyama, Akira; Okamura, Gensuke; Goshima, Atsushi; Miura, Taihei; Kurihara, Takuya; Fukuda, Yuji; Kanamoto, Takashi; Nakata, Ken; Okada, Seiji; Ebina, Kosuke

doi:https://doi.org/10.1172/jci.insight.171962

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice

Takami, Kenji; Okamoto, Kazuki; Etani, Yuki et al.

JCI Insight, 2023, 8(22), e171962

Number of Access:1,613（2025-07-10 13:13 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93384

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Title	Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice
Creator	CreatorName Takami, Kenji
	NRID 1000040177085 1000040177085 CreatorName Okamoto, Kazuki
	NRID 1000060898930 1000060898930 ORCID 0000-0001-5741-5969 0000-0001-5741-5969 researchmap permalink Yetani0302 Yetani0302 CreatorName Etani, Yuki
	NRID 1000010527708 1000010527708 CreatorName Hirao, Makoto
	CreatorName Miyama, Akira
	CreatorName Okamura, Gensuke
	CreatorName Goshima, Atsushi
	CreatorName Miura, Taihei
	CreatorName Kurihara, Takuya
	CreatorName Fukuda, Yuji
	NRID 1000020512049 1000020512049 researchmap permalink kanamoto kanamoto Scopus Author ID 7005012135 7005012135 CreatorName Kanamoto, Takashi
	NRID 1000000283747 1000000283747 researchmap permalink ken-nakata ken-nakata Scopus Author ID 7402151308 7402151308 CreatorName Nakata, Ken
	NRID 1000030448435 1000030448435 ORCID 0000-0002-5107-8209 0000-0002-5107-8209 researchmap permalink okadaseiji okadaseiji Scopus Author ID 35079139100 35079139100 CreatorName Okada, Seiji
	NRID 1000070612076 1000070612076 researchmap permalink k-ebina k-ebina Scopus Author ID 8415453300 8415453300 ORCID 0000-0002-2426-1024 0000-0002-2426-1024 CreatorName Ebina, Kosuke
Description	Takami K., Okamoto K., Etani Y., et al. Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice. JCI Insight 8, e171962 (2023); https://doi.org/10.1172/jci.insight.171962.
Abstract	NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.
Publisher	American Society for Clinical Investigation
Source Title	JCI Insight
Volume (Issue)	8(22)
Page	e171962
Date of Issued	2023-12-04
Language	English
Handle URL	https://hdl.handle.net/11094/93384
eISSN	23793708
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1172/jci.insight.171962
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

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Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	JCI Insight. 2023, 8(22), p. e171962
DC.title	Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice
DC.creator	Takami, Kenji
	Okamoto, Kazuki
	Etani, Yuki
	Hirao, Makoto
	Miyama, Akira
	Okamura, Gensuke
	Goshima, Atsushi
	Miura, Taihei
	Kurihara, Takuya
	Fukuda, Yuji
	Kanamoto, Takashi
	Nakata, Ken
	Okada, Seiji
	Ebina, Kosuke
DC.publisher	American Society for Clinical Investigation
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-04
DC.identifier	https://doi.org/10.1172/jci.insight.171962
DC.description	Takami K., Okamoto K., Etani Y., et al. Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice. JCI Insight 8, e171962 (2023); https://doi.org/10.1172/jci.insight.171962.
DCTERMS.abstract	NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93384
citation_title	Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice
citation_author	Takami, Kenji
	Okamoto, Kazuki
	Etani, Yuki
	Hirao, Makoto
	Miyama, Akira
	Okamura, Gensuke
	Goshima, Atsushi
	Miura, Taihei
	Kurihara, Takuya
	Fukuda, Yuji
	Kanamoto, Takashi
	Nakata, Ken
	Okada, Seiji
	Ebina, Kosuke
citation_publisher	American Society for Clinical Investigation
citation_language	English
citation_date	2023-12-04
citation_journal_title	JCI Insight
citation_volume	8
citation_issue	22
citation_firstpage	e171962
citation_doi	https://doi.org/10.1172/jci.insight.171962
citation_public_url	https://hdl.handle.net/11094/93384