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Full Length Article | Open Access

Single-cell transcriptomic analysis of chondrocytes in cartilage and pathogenesis of osteoarthritis

Changyuan Huanga,b,1, Bin Zengc,d,1, Bo Zhoub, Guanming Chenb, Qi Zhangb, Wenhong Houb,e, Guozhi Xiaof, Li Duanc( ), Ni Hongb( ), Wenfei Jing,2( )
Harbin Institute of Technology, Harbin, Heilongjiang 150001, China
School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
Department of Orthopedics, Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform, Guangdong Artificial Intelligence Biomedical Innovation Platform, Shenzhen Second People’s Hospital, The First Affiliated Hospital, Shenzhen University, Shenzhen, Guangdong 518035, China
Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi 53020, China
The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong 523710, China
Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen, Guangdong 518055, China
CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Peer review under responsibility of Chongqing Medical University.

1 These authors contributed equally to this work.

2 Lead contact.

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Abstract

Chondrocyte is considered the only cell type in cartilage. However, the cell heterogeneity of chondrocytes in human articular cartilage is still not well defined, which hinders our understanding of the pathogenesis of osteoarthritis (OA). Here, we constructed a single-cell transcriptomic atlas of chondrocytes in healthy cartilage and identified nine chondrocyte subsets including homeostatic chondrocytes, proliferate fibrochondrocytes, and hypertrophic chondrocytes (HTC). Interestingly, we identified two distinct HTC subpopulations, among which HTC-1 specifically expressed genes associated with apoptosis and programmed cell death. We identified two main trajectories of chondrocytes, one of which differentiates into fibrochondrocytes, while the other terminates in apoptosis. Comparison of chondrocyte subsets between healthy and OA cartilage showed that proliferate fibrochondrocytes and HTC-1 expanded in OA patients, whereas homeostatic chondrocytes decreased. Interestingly, we discovered an OA-specific proliferate fibrochondrocyte subset that may contribute to the development of OA via inflammation. In summary, this study significantly enhanced our understanding of cell heterogeneity of chondrocytes in articular cartilage and provides insight into the pathogenesis of OA.

Keywords

Cell heterogeneityChondrocyte apoptosisChondrocyte differentiationChondrocyte fibrosisOsteoarthritisSingle-cell RNA-seq

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Genes & Diseases
Volume 12 Issue 2,
March 2025
Article number: 101241
DOI: 10.1016/j.gendis.2024.101241
Cite this article:
Huang C, Zeng B, Zhou B, et al. Single-cell transcriptomic analysis of chondrocytes in cartilage and pathogenesis of osteoarthritis. Genes & Diseases, 2025, 12(2): 101241. https://doi.org/10.1016/j.gendis.2024.101241

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Received: 29 August 2023
Revised: 26 December 2023
Accepted: 31 December 2023
Published: 02 February 2024
© 2024 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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