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

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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.
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Category
学術雑誌論文 Journal Article