Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro

Miyama, Akira; Ebina, Kosuke; Hirao, Makoto; Okamura, Gensuke; Etani, Yuki; Takami, Kenji; Goshima, Atsushi; Miura, Taihei; Oyama, Shohei; Kanamoto, Takashi; Yoshikawa, Hideki; Nakata, Ken

doi:https://doi.org/10.1007/s00774-021-01206-5

Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro

Miyama, Akira; Ebina, Kosuke; Hirao, Makoto et al.

Journal of Bone and Mineral Metabolism, 2021, 39(4), 639-648

Number of Access:1,367（2025-09-03 11:38 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93247

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Title	Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro
Creator	CreatorName Miyama, Akira
	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 Okamura, Gensuke
	NRID 1000060898930 1000060898930 ORCID 0000-0001-5741-5969 0000-0001-5741-5969 researchmap permalink Yetani0302 Yetani0302 CreatorName Etani, Yuki
	CreatorName Takami, Kenji
	CreatorName Goshima, Atsushi
	CreatorName Miura, Taihei
	CreatorName Oyama, Shohei
	CreatorName Kanamoto, Takashi
	CreatorName Yoshikawa, Hideki
	NRID 1000000283747 1000000283747 researchmap permalink ken-nakata ken-nakata Scopus Author ID 7402151308 7402151308 CreatorName Nakata, Ken
Subject	Glucocorticoid-induced osteoporosis
	Iguratimod
	Osteoblast
	Osteoclast
	Osteocyte
Description	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00774-021-01206-5
Description	Miyama A., Ebina K., Hirao M., et al. Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro. Journal of Bone and Mineral Metabolism 39, 639 (2021)
Abstract	Introduction: Glucocorticoids are widely used to treat various diseases including rheumatoid arthritis (RA); however, one of the most frequent and severe adverse effects is glucocorticoid-induced osteoporosis (GIOP). Iguratimod (IGU) is a novel conventional synthetic disease-modifying anti-rheumatic drug developed in Japan. The aim of this study is to investigate the effects of IGU on glucocorticoid-induced disorder of bone metabolism in vitro. Materials and methods: In osteoclastogenesis of mouse bone marrow-derived cells, tartrate-resistant acid phosphatase staining, resorption pit assay, western blotting, real-time polymerase chain reaction (PCR), and mRNA sequencing were performed. In osteoblastogenesis of MC3T3-E1 cells, alkaline phosphatase (ALP) staining and activity, alizarin red staining, and mRNA sequencing were performed, and real-time PCR and western blotting were conducted in MC3T3-E1 cells and murine osteocyte-like cell line MLO-Y4 cells. Results: IGU significantly suppressed a dexamethasone-induced increase in osteoclasts, differentiation, and bone resorption activity by inhibition of the receptor activator of the nuclear factor kappa-B (RANK)/tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)/nuclear factor kappa-B (NFκB)-p52 pathway. In MC3T3-E1 cells, IGU significantly upregulated dexamethasone-induced downregulation of ALP activity, bone mineralization, and osteoblast-related gene and protein expression. In MLO-Y4 cells, IGU significantly upregulated dexamethasone-induced downregulation of the gene expression of ALP and osteocalcin, and also downregulated receptor activator of NFκB ligand (RANKL)/osteoprotegerin gene expression ratio without dexamethasone. Conclusion: These results suggest that IGU may improve glucocorticoid-induced disorder of bone metabolism and may exhibit positive effects against GIOP associated with RA.
Publisher	Springer Japan
Source Title	Journal of Bone and Mineral Metabolism
Volume (Issue)	39(4)
Page	639-648
Date of Issued	2021-07-01
Language	English
Handle URL	https://hdl.handle.net/11094/93247
PISSN	09148779
eISSN	14355604
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1007/s00774-021-01206-5
Access Rights	open access
CopyRight	© 2021, The Japanese Society Bone and Mineral Research.
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	Journal of Bone and Mineral Metabolism. 2021, 39(4), p. 639-648
DC.title	Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro
DC.creator	Miyama, Akira
	Ebina, Kosuke
	Hirao, Makoto
	Okamura, Gensuke
	Etani, Yuki
	Takami, Kenji
	Goshima, Atsushi
	Miura, Taihei
	Oyama, Shohei
	Kanamoto, Takashi
	Yoshikawa, Hideki
	Nakata, Ken
DC.publisher	Springer Japan
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2021-07-01
DC.identifier	https://doi.org/10.1007/s00774-021-01206-5
DC.subject	Glucocorticoid-induced osteoporosis
	Iguratimod
	Osteoblast
	Osteoclast
	Osteocyte
DC.description	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00774-021-01206-5
DC.description	Miyama A., Ebina K., Hirao M., et al. Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro. Journal of Bone and Mineral Metabolism 39, 639 (2021)
DCTERMS.abstract	Introduction: Glucocorticoids are widely used to treat various diseases including rheumatoid arthritis (RA); however, one of the most frequent and severe adverse effects is glucocorticoid-induced osteoporosis (GIOP). Iguratimod (IGU) is a novel conventional synthetic disease-modifying anti-rheumatic drug developed in Japan. The aim of this study is to investigate the effects of IGU on glucocorticoid-induced disorder of bone metabolism in vitro. Materials and methods: In osteoclastogenesis of mouse bone marrow-derived cells, tartrate-resistant acid phosphatase staining, resorption pit assay, western blotting, real-time polymerase chain reaction (PCR), and mRNA sequencing were performed. In osteoblastogenesis of MC3T3-E1 cells, alkaline phosphatase (ALP) staining and activity, alizarin red staining, and mRNA sequencing were performed, and real-time PCR and western blotting were conducted in MC3T3-E1 cells and murine osteocyte-like cell line MLO-Y4 cells. Results: IGU significantly suppressed a dexamethasone-induced increase in osteoclasts, differentiation, and bone resorption activity by inhibition of the receptor activator of the nuclear factor kappa-B (RANK)/tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)/nuclear factor kappa-B (NFκB)-p52 pathway. In MC3T3-E1 cells, IGU significantly upregulated dexamethasone-induced downregulation of ALP activity, bone mineralization, and osteoblast-related gene and protein expression. In MLO-Y4 cells, IGU significantly upregulated dexamethasone-induced downregulation of the gene expression of ALP and osteocalcin, and also downregulated receptor activator of NFκB ligand (RANKL)/osteoprotegerin gene expression ratio without dexamethasone. Conclusion: These results suggest that IGU may improve glucocorticoid-induced disorder of bone metabolism and may exhibit positive effects against GIOP associated with RA.
DC.rights	© 2021, The Japanese Society Bone and Mineral Research.
DC.format	93247
citation_title	Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro
citation_author	Miyama, Akira
	Ebina, Kosuke
	Hirao, Makoto
	Okamura, Gensuke
	Etani, Yuki
	Takami, Kenji
	Goshima, Atsushi
	Miura, Taihei
	Oyama, Shohei
	Kanamoto, Takashi
	Yoshikawa, Hideki
	Nakata, Ken
citation_publisher	Springer Japan
citation_language	English
citation_date	2021-07-01
citation_journal_title	Journal of Bone and Mineral Metabolism
citation_volume	39
citation_issue	4
citation_firstpage	639
citation_lastpage	648
citation_doi	https://doi.org/10.1007/s00774-021-01206-5
citation_public_url	https://hdl.handle.net/11094/93247

Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro

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