Abstract

Objectives

Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.

Methods

Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies.

Results

We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype.

Conclusions

Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.

Details

Title
Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
Author
Fan, Yue 1   VIAFID ORCID Logo  ; Bian, Xuzhao 2 ; Meng, Xiaogao 3 ; Li, Lei 2 ; Fu, Laiyi 4 ; Zhang, Yanan 2 ; Wang, Long 5 ; Zhang, Yan 6 ; Gao, Dalong 7 ; Guo, Xiong 8 ; Lammi, Mikko Juhani 9   VIAFID ORCID Logo  ; Peng, Guangdun 10 ; Sun, Shiquan 1 

1  Center for Single-Cell Omics and Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China; Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Shaanxi Province; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an Jiaotong University, Xi'an, Shaanxi, China 
2  Center for Single-Cell Omics and Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China 
3  Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; Center for Cell Lineage and Development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China 
4  School of Automation Science and Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China 
5  Center for Single-Cell Omics and Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China; Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China 
6  Center for Single-Cell Omics and Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China; Department of Orthopaedics, Honghui Hospital, Xi'an, Shaanxi, China 
7  Department of Orthopaedics, The Central Hospital of Xianyang, Xianyang, China 
8  Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Shaanxi Province; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi, China 
9  Department of Integrative Medical Biology, University of Umeå, Umeå, Sweden 
10  Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Center for Cell Lineage and Development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China; University of Chinese Academy of Sciences, Beijing, China 
First page
ard-2023-224420
Section
Osteoarthritis
Publication year
2024
Publication date
Feb 2024
Publisher
Elsevier Limited
ISSN
00034967
e-ISSN
14682060
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1136/ard-2023-224420
ProQuest document ID
2923008785
Copyright
© 2024 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.