Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone

Hagizawa, Hiroki; Koyamatsu, Saeko; Okada, Seiji; Kaito, Takashi; Tsumaki, Noriyuki

doi:https://doi.org/10.3389/fcell.2023.1151947

Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone

Hagizawa, Hiroki; Koyamatsu, Saeko; Okada, Seiji et al.

Frontiers in Cell and Developmental Biology, 2023, 11, 1151947

Number of Access:968（2025-11-23 22:45 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93296

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Title	Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone
Creator	CreatorName Hagizawa, Hiroki
	CreatorName Koyamatsu, Saeko
	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 1000070623982 1000070623982 ORCID 0000-0003-4882-2997 0000-0003-4882-2997 researchmap permalink 911_0 911_0 Scopus Author ID 25824322100 25824322100 CreatorName Kaito, Takashi
	NRID 1000050303938 1000050303938 ORCID 0000-0002-0520-3654 0000-0002-0520-3654 researchmap permalink cart cart Scopus Author ID 7004069586 7004069586 CreatorName Tsumaki, Noriyuki
Subject	chondrocytes
	hedgehog
	HIF-1α
	nucleus pulposus cells
	single-cell RNA sequencing
Description	Hagizawa H., Koyamatsu S., Okada S., et al. Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone. Frontiers in Cell and Developmental Biology 11, 1151947 (2023); https://doi.org/10.3389/fcell.2023.1151947.
Abstract	Objective: The nucleus pulposus (NP) comprises notochordal NP cells (NCs) and chondrocyte-like NP cells (CLCs). Although morphological similarities between CLCs and chondrocytes have been reported, interactions between CLCs and NCs remain unclear. In this study, we aimed to clarify regulatory mechanisms of cells in the NP and chondrocytes. Design: We performed single-cell RNA sequencing (scRNA-seq) analysis of the articular cartilage (AC) and NP of three-year-old cynomolgus monkeys in which NCs were present. We then performed immunohistochemical analysis of NP and distal femur. We added sonic hedgehog (SHH) to primary chondrocyte culture. Results: The scRNA-seq analysis revealed that CLCs and some articular chondrocytes had similar gene expression profiles, particularly related to GLI1, the nuclear mediator of the hedgehog pathway. In the NP, cell–cell interaction analysis revealed SHH expression in NCs, resulting in hedgehog signaling to CLCs. In contrast, no hedgehog ligands were expressed by chondrocytes in AC samples. Immunohistochemical analysis of the distal end of femur indicated that SHH and Indian hedgehog (IHH) were expressed around the subchondral bone that was excluded from our scRNA-seq sample. scRNA-seq data analysis and treatment of primary chondrocytes with SHH revealed that hedgehog proteins mediated an increase in hypoxia-inducible factor 1-alpha (HIF-1α) levels. Conclusion: CLCs and some articular chondrocytes have similar transcriptional profiles, regulated by paracrine hedgehog proteins secreted from NCs in the NP and from the subchondral bone in the AC to promote the HIF-1α pathway.
Publisher	Frontiers Media SA
Source Title	Frontiers in Cell and Developmental Biology
Volume (Issue)	11
Page	1151947
Date of Issued	2023-05-15
Language	English
Handle URL	https://hdl.handle.net/11094/93296
eISSN	2296634X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.3389/fcell.2023.1151947
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

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Frontiers in Cell and Developmental Biology. 2023, 11, p. 1151947
DC.title	Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone
DC.creator	Hagizawa, Hiroki
	Koyamatsu, Saeko
	Okada, Seiji
	Kaito, Takashi
	Tsumaki, Noriyuki
DC.publisher	Frontiers Media SA
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-05-15
DC.identifier	https://doi.org/10.3389/fcell.2023.1151947
DC.subject	chondrocytes
	hedgehog
	HIF-1α
	nucleus pulposus cells
	single-cell RNA sequencing
DC.description	Hagizawa H., Koyamatsu S., Okada S., et al. Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone. Frontiers in Cell and Developmental Biology 11, 1151947 (2023); https://doi.org/10.3389/fcell.2023.1151947.
DCTERMS.abstract	Objective: The nucleus pulposus (NP) comprises notochordal NP cells (NCs) and chondrocyte-like NP cells (CLCs). Although morphological similarities between CLCs and chondrocytes have been reported, interactions between CLCs and NCs remain unclear. In this study, we aimed to clarify regulatory mechanisms of cells in the NP and chondrocytes. Design: We performed single-cell RNA sequencing (scRNA-seq) analysis of the articular cartilage (AC) and NP of three-year-old cynomolgus monkeys in which NCs were present. We then performed immunohistochemical analysis of NP and distal femur. We added sonic hedgehog (SHH) to primary chondrocyte culture. Results: The scRNA-seq analysis revealed that CLCs and some articular chondrocytes had similar gene expression profiles, particularly related to GLI1, the nuclear mediator of the hedgehog pathway. In the NP, cell–cell interaction analysis revealed SHH expression in NCs, resulting in hedgehog signaling to CLCs. In contrast, no hedgehog ligands were expressed by chondrocytes in AC samples. Immunohistochemical analysis of the distal end of femur indicated that SHH and Indian hedgehog (IHH) were expressed around the subchondral bone that was excluded from our scRNA-seq sample. scRNA-seq data analysis and treatment of primary chondrocytes with SHH revealed that hedgehog proteins mediated an increase in hypoxia-inducible factor 1-alpha (HIF-1α) levels. Conclusion: CLCs and some articular chondrocytes have similar transcriptional profiles, regulated by paracrine hedgehog proteins secreted from NCs in the NP and from the subchondral bone in the AC to promote the HIF-1α pathway.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93296
citation_title	Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone
citation_author	Hagizawa, Hiroki
	Koyamatsu, Saeko
	Okada, Seiji
	Kaito, Takashi
	Tsumaki, Noriyuki
citation_publisher	Frontiers Media SA
citation_language	English
citation_date	2023-05-15
citation_journal_title	Frontiers in Cell and Developmental Biology
citation_volume	11
citation_firstpage	1151947
citation_doi	https://doi.org/10.3389/fcell.2023.1151947
citation_public_url	https://hdl.handle.net/11094/93296

Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone

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