Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway

Goshima, Atsushi; Etani, Yuki; Hirao, Makoto; Yamakawa, Satoshi; Okamura, Gensuke; Miyama, Akira; Takami, Kenji; Miura, Taihei; Fukuda, Yuji; Kurihara, Takuya; Ochiai, Nagahiro; Oyama, Shohei; Otani, Shunya; Tamaki, Masashi; Ishibashi, Teruya; Tomita, Tetsuya; Kanamoto, Takashi; Nakata, Ken; Okada, Seiji; Ebina, Kosuke

doi:https://doi.org/10.1016/j.joca.2023.07.010

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway

Goshima, Atsushi; Etani, Yuki; Hirao, Makoto et al.

Osteoarthritis and Cartilage, 2023, 31(12), 1581-1593

Number of Access:1,801（2025-07-24 02:11 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93241

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Title	Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway
Creator	CreatorName Goshima, Atsushi
	NRID 1000060898930 1000060898930 CreatorName Etani, Yuki
	NRID 1000010527708 1000010527708 CreatorName Hirao, Makoto
	NRID 1000040816740 1000040816740 researchmap permalink satyamakawa satyamakawa CreatorName Yamakawa, Satoshi
	CreatorName Okamura, Gensuke
	CreatorName Miyama, Akira
	CreatorName Takami, Kenji
	CreatorName Miura, Taihei
	CreatorName Fukuda, Yuji
	CreatorName Kurihara, Takuya
	CreatorName Ochiai, Nagahiro
	CreatorName Oyama, Shohei
	CreatorName Otani, Shunya
	NRID 1000090837535 1000090837535 ORCID 0000-0003-4942-7446 0000-0003-4942-7446 researchmap permalink masashitamaki masashitamaki Scopus Author ID 35312671400 35312671400 CreatorName Tamaki, Masashi
	CreatorName Ishibashi, Teruya
	NRID 1000030283766 1000030283766 CreatorName Tomita, Tetsuya
	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
Subject	Basic fibroblast growth factor
	CXCL6
	CXCR2
	Meniscus regeneration
	Synovial mesenchymal stem cells
Description	Goshima A., Etani Y., Hirao M., et al. Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway. Osteoarthritis and Cartilage , (2023); https://doi.org/10.1016/j.joca.2023.07.010.
Abstract	Objective: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. Methods: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (−) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. Results: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. Conclusion: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.
Publisher	Elsevier
Source Title	Osteoarthritis and Cartilage
Volume (Issue)	31(12)
Page	1581-1593
Date of Issued	2023-12-01
Language	English
Handle URL	https://hdl.handle.net/11094/93241
PISSN	10634584
eISSN	15229653
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1016/j.joca.2023.07.010
Access Rights	open access
CopyRight	© 2023. 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	Osteoarthritis and Cartilage. 2023, 31(12), p. 1581-1593
DC.title	Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway
DC.creator	Goshima, Atsushi
	Etani, Yuki
	Hirao, Makoto
	Yamakawa, Satoshi
	Okamura, Gensuke
	Miyama, Akira
	Takami, Kenji
	Miura, Taihei
	Fukuda, Yuji
	Kurihara, Takuya
	Ochiai, Nagahiro
	Oyama, Shohei
	Otani, Shunya
	Tamaki, Masashi
	Ishibashi, Teruya
	Tomita, Tetsuya
	Kanamoto, Takashi
	Nakata, Ken
	Okada, Seiji
	Ebina, Kosuke
DC.publisher	Elsevier
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-01
DC.identifier	https://doi.org/10.1016/j.joca.2023.07.010
DC.subject	Basic fibroblast growth factor
	CXCL6
	CXCR2
	Meniscus regeneration
	Synovial mesenchymal stem cells
DC.description	Goshima A., Etani Y., Hirao M., et al. Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway. Osteoarthritis and Cartilage , (2023); https://doi.org/10.1016/j.joca.2023.07.010.
DCTERMS.abstract	Objective: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. Methods: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (−) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. Results: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. Conclusion: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.
DC.rights	© 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
DC.format	93241
citation_title	Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway
citation_author	Goshima, Atsushi
	Etani, Yuki
	Hirao, Makoto
	Yamakawa, Satoshi
	Okamura, Gensuke
	Miyama, Akira
	Takami, Kenji
	Miura, Taihei
	Fukuda, Yuji
	Kurihara, Takuya
	Ochiai, Nagahiro
	Oyama, Shohei
	Otani, Shunya
	Tamaki, Masashi
	Ishibashi, Teruya
	Tomita, Tetsuya
	Kanamoto, Takashi
	Nakata, Ken
	Okada, Seiji
	Ebina, Kosuke
citation_publisher	Elsevier
citation_language	English
citation_date	2023-12-01
citation_journal_title	Osteoarthritis and Cartilage
citation_volume	31
citation_issue	12
citation_firstpage	1581
citation_lastpage	1593
citation_doi	https://doi.org/10.1016/j.joca.2023.07.010
citation_public_url	https://hdl.handle.net/11094/93241

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway

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