Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells

Rui, Shumin; Kubota, Takuo; Ohata, Yasuhisa; Yamamoto, Kenichi; Fujiwara, Makoto; Takeyari, Shinji; Ozono, Keiichi

doi:https://doi.org/10.1016/j.bone.2022.116525

Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells

Rui, Shumin; Kubota, Takuo; Ohata, Yasuhisa et al.

Bone, 2022, 164, 116525

アクセス数:1,733件（2026-04-04 22:19 集計）

固定URL: https://hdl.handle.net/11094/89423

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タイトル	Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells
著者	著者名 Rui, Shumin
	NRID 1000040629135 1000040629135 ORCID 0000-0003-4483-4405 0000-0003-4483-4405 researchmap permalink k_b_t k_b_t Scopus Author ID 8236245700 8236245700 著者名 Kubota, Takuo
	NRID 1000020805460 1000020805460 ORCID 0000-0001-6084-6620 0000-0001-6084-6620 researchmap permalink pedmed pedmed Scopus Author ID 25626528000 25626528000 著者名 Ohata, Yasuhisa
	著者名 Yamamoto, Kenichi
	NRID 1000050625697 1000050625697 ORCID 0000-0002-6799-9774 0000-0002-6799-9774 researchmap permalink makofuji1977 makofuji1977 Scopus Author ID 57203794801 57203794801 著者名 Fujiwara, Makoto
	NRID 1000070774454 1000070774454 ORCID 0000-0002-3627-1932 0000-0002-3627-1932 researchmap permalink shinji_takeyari shinji_takeyari Scopus Author ID 56058943900 56058943900 著者名 Takeyari, Shinji
	NRID 1000020270770 1000020270770 researchmap permalink read0092357 read0092357 Scopus Author ID 55545335700 55545335700 著者名 Ozono, Keiichi
キーワード等	Phosphate
	Non-canonical Wnt signaling pathway
	WNT5b
	Osteogenic differentiation
	Human mesenchymal stem cells
内容	Shumin Rui, Takuo Kubota, Yasuhisa Ohata, Kenichi Yamamoto, Makoto Fujiwara, Shinji Takeyari, Keiichi Ozono, Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells, Bone, 2022, 164, 16525.
抄録	Background: Phosphate is indispensable in osteogenesis and mineralization. However, mechanisms by which phosphate enhances osteogenic differentiation are not fully understood. In this study, we studied the effect of phosphate on osteogenic differentiation as well as signaling pathways induced by phosphate in the process. Method: Induced human bone marrow-derived mesenchymal stem cells differentiation into osteoblasts by the change of media containing β-glycerophosphate (GP), 1 mM inorganic phosphate, or 3 mM inorganic phosphate (Pi). The differentiation of osteoblasts was verified by the expression of osteoblast differentiation markers and calcium deposition. RNA sequencing was performed to assess transcriptome in the early stage of osteogenic differentiation. Results: Osteogenic differentiation and mineralization were promoted in the 3 mM Pi group compared to those in the GP and 1 mM Pi groups on day 7 of culture. RNA sequencing revealed that the gene expressions involved in osteogenesis and the components in the Wnt signaling pathway was increased in 3 mM Pi group compared with those in the GP on day 7. Analysis with qPCR and Western blot suggested upregulation of components in the non-canonical Wnt signaling pathway, including WNT5b and phosphorylated-c-Jun in the 3 mM Pi group on day 7. WNT11 mRNA expression was increased in the 2 induction groups on day 7. Inhibition of WNT5b by siRNA experiment attenuated the components in non-canonical Wnt signaling expression, including WNT5b, WNT11 and ROR2 mRNA expression and phosphorylated-c-Jun protein expression. In addition, osteogenic differentiation and mineralization were partly decreased in 3 mM Pi group on day 7 by the inhibition of WNT5b. Conclusion: Pi promoted osteogenic differentiation through the up-regulation of the non-canonical Wnt signaling pathway, including WNT5b, WNT11, p-c-Jun/c-Jun, in the early stage of differentiation. These findings provide a new perspective into the association of Pi and the non-canonical Wnt signaling pathway during osteogenic differentiation.
出版者	Elsevier
収録物名	Bone
巻(号)	164
ページ	116525
刊行年月	2022-11
言語	英語
ハンドルURL	https://hdl.handle.net/11094/89423
PISSN	87563282
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1016/j.bone.2022.116525
アクセス権	open access
権利情報	©2022. This manuscript version is made available under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Accepted Manuscript
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	Bone. 2022, 164, p. 116525
DC.title	Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells
DC.creator	Rui, Shumin
	Kubota, Takuo
	Ohata, Yasuhisa
	Yamamoto, Kenichi
	Fujiwara, Makoto
	Takeyari, Shinji
	Ozono, Keiichi
DC.publisher	Elsevier
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2022-11
DC.identifier	https://doi.org/10.1016/j.bone.2022.116525
DC.subject	Phosphate
	Non-canonical Wnt signaling pathway
	WNT5b
	Osteogenic differentiation
	Human mesenchymal stem cells
DC.description	Shumin Rui, Takuo Kubota, Yasuhisa Ohata, Kenichi Yamamoto, Makoto Fujiwara, Shinji Takeyari, Keiichi Ozono, Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells, Bone, 2022, 164, 16525.
DCTERMS.abstract	Background: Phosphate is indispensable in osteogenesis and mineralization. However, mechanisms by which phosphate enhances osteogenic differentiation are not fully understood. In this study, we studied the effect of phosphate on osteogenic differentiation as well as signaling pathways induced by phosphate in the process. Method: Induced human bone marrow-derived mesenchymal stem cells differentiation into osteoblasts by the change of media containing β-glycerophosphate (GP), 1 mM inorganic phosphate, or 3 mM inorganic phosphate (Pi). The differentiation of osteoblasts was verified by the expression of osteoblast differentiation markers and calcium deposition. RNA sequencing was performed to assess transcriptome in the early stage of osteogenic differentiation. Results: Osteogenic differentiation and mineralization were promoted in the 3 mM Pi group compared to those in the GP and 1 mM Pi groups on day 7 of culture. RNA sequencing revealed that the gene expressions involved in osteogenesis and the components in the Wnt signaling pathway was increased in 3 mM Pi group compared with those in the GP on day 7. Analysis with qPCR and Western blot suggested upregulation of components in the non-canonical Wnt signaling pathway, including WNT5b and phosphorylated-c-Jun in the 3 mM Pi group on day 7. WNT11 mRNA expression was increased in the 2 induction groups on day 7. Inhibition of WNT5b by siRNA experiment attenuated the components in non-canonical Wnt signaling expression, including WNT5b, WNT11 and ROR2 mRNA expression and phosphorylated-c-Jun protein expression. In addition, osteogenic differentiation and mineralization were partly decreased in 3 mM Pi group on day 7 by the inhibition of WNT5b. Conclusion: Pi promoted osteogenic differentiation through the up-regulation of the non-canonical Wnt signaling pathway, including WNT5b, WNT11, p-c-Jun/c-Jun, in the early stage of differentiation. These findings provide a new perspective into the association of Pi and the non-canonical Wnt signaling pathway during osteogenic differentiation.
DC.rights	©2022. This manuscript version is made available under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	89423
citation_title	Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells
citation_author	Rui, Shumin
	Kubota, Takuo
	Ohata, Yasuhisa
	Yamamoto, Kenichi
	Fujiwara, Makoto
	Takeyari, Shinji
	Ozono, Keiichi
citation_publisher	Elsevier
citation_language	英語
citation_date	2022-11
citation_journal_title	Bone
citation_volume	164
citation_firstpage	116525
citation_doi	https://doi.org/10.1016/j.bone.2022.116525
citation_public_url	https://hdl.handle.net/11094/89423

Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells

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