Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice

Noguchi, Takaaki; Ebina, Kosuke; Hirao, Makoto; Kawase, Ryota; Ohama, Tohru; Yamashita, Shizuya; Morimoto, Tokimitsu; Koizumi, Kota; Kitaguchi, Kazuma; Matsuoka, Hozo; Kaneshiro, Shoichi; Yoshikawa, Hideki

doi:https://doi.org/10.1016/j.bbrc.2015.08.077

Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice

Noguchi, Takaaki; Ebina, Kosuke; Hirao, Makoto et al.

Biochemical and Biophysical Research Communications, 2015, 465(3), 638-643

Number of Access:771（2025-09-03 11:38 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93267

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Title	Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice
Creator	CreatorName Noguchi, Takaaki
	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
	NRID 1000010527708 1000010527708 CreatorName Hirao, Makoto
	CreatorName Kawase, Ryota
	NRID 1000020467583 1000020467583 researchmap permalink pqrst-2011xyz3116 pqrst-2011xyz3116 Scopus Author ID 7005598644 7005598644 CreatorName Ohama, Tohru
	CreatorName Yamashita, Shizuya
	CreatorName Morimoto, Tokimitsu
	CreatorName Koizumi, Kota
	CreatorName Kitaguchi, Kazuma
	CreatorName Matsuoka, Hozo
	CreatorName Kaneshiro, Shoichi
	NRID 1000060191558 1000060191558 CreatorName Yoshikawa, Hideki
Subject	Bone metabolism
	ERK1/2
	Osteoblast
	Osteoclast
	Progranulin
	TNF-α
Description	Noguchi T., Ebina K., Hirao M., et al. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Biochemical and Biophysical Research Communications 465, 638 (2015); https://doi.org/10.1016/j.bbrc.2015.08.077.
Abstract	A close correlation between atherosclerosis, inflammation, and osteoporosis has been recognized, although the precise mechanism remains unclear. The growth factor progranulin (PGRN) is expressed in various cells such as macrophages, leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases, such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-α (TNF-α) signaling. The purpose of this study was to investigate the effect of PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%): 5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In vitro, PGRN inhibited TNF-α-induced osteoclastogenesis from spleen cells of PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast-related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up-regulated osteoblastic differentiation by down-regulating phosphorylation of ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment target for both atherosclerosis and inflammation-related osteoporosis.
Publisher	Academic Press Inc
Source Title	Biochemical and Biophysical Research Communications
Volume (Issue)	465(3)
Page	638-643
Date of Issued	2015-09-25
Language	English
Handle URL	https://hdl.handle.net/11094/93267
PISSN	0006291X
eISSN	10902104
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1016/j.bbrc.2015.08.077
Access Rights	open access
CopyRight	© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Biochemical and Biophysical Research Communications. 2015, 465(3), p. 638-643
DC.title	Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice
DC.creator	Noguchi, Takaaki
	Ebina, Kosuke
	Hirao, Makoto
	Kawase, Ryota
	Ohama, Tohru
	Yamashita, Shizuya
	Morimoto, Tokimitsu
	Koizumi, Kota
	Kitaguchi, Kazuma
	Matsuoka, Hozo
	Kaneshiro, Shoichi
	Yoshikawa, Hideki
DC.publisher	Academic Press Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2015-09-25
DC.identifier	https://doi.org/10.1016/j.bbrc.2015.08.077
DC.subject	Bone metabolism
	ERK1/2
	Osteoblast
	Osteoclast
	Progranulin
	TNF-α
DC.description	Noguchi T., Ebina K., Hirao M., et al. Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice. Biochemical and Biophysical Research Communications 465, 638 (2015); https://doi.org/10.1016/j.bbrc.2015.08.077.
DCTERMS.abstract	A close correlation between atherosclerosis, inflammation, and osteoporosis has been recognized, although the precise mechanism remains unclear. The growth factor progranulin (PGRN) is expressed in various cells such as macrophages, leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases, such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-α (TNF-α) signaling. The purpose of this study was to investigate the effect of PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%): 5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In vitro, PGRN inhibited TNF-α-induced osteoclastogenesis from spleen cells of PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast-related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up-regulated osteoblastic differentiation by down-regulating phosphorylation of ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment target for both atherosclerosis and inflammation-related osteoporosis.
DC.rights	© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
DC.format	93267
citation_title	Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice
citation_author	Noguchi, Takaaki
	Ebina, Kosuke
	Hirao, Makoto
	Kawase, Ryota
	Ohama, Tohru
	Yamashita, Shizuya
	Morimoto, Tokimitsu
	Koizumi, Kota
	Kitaguchi, Kazuma
	Matsuoka, Hozo
	Kaneshiro, Shoichi
	Yoshikawa, Hideki
citation_publisher	Academic Press Inc
citation_language	English
citation_date	2015-09-25
citation_journal_title	Biochemical and Biophysical Research Communications
citation_volume	465
citation_issue	3
citation_firstpage	638
citation_lastpage	643
citation_doi	https://doi.org/10.1016/j.bbrc.2015.08.077
citation_public_url	https://hdl.handle.net/11094/93267

Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice

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