Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression.

Wenzhou Liu,Weidong Song,Mengjun Ma,Shuting Yang,Yanbo Chen,Tao Yang,Gang Zeng

doi:10.3389/fmolb.2021.748360

Abstract

Objective: Osteoarthritis (OA) is the most common chronic degenerative joint disease, which represents the leading cause of age-related disability. Here, this study aimed to depict the intercellular heterogeneity of OA synovial tissues. Methods: Single-cell RNA sequencing (scRNA-seq) data were preprocessed and quality controlled by the Seurat package. Cell cluster was presented and cell types were annotated based on the mRNA expression of corresponding marker genes by the SingleR package. Cell-cell communication was assessed among different cell types. After integrating the GSE55235 and GSE55457 datasets, differentially expressed genes were identified between OA and normal synovial tissues. Then, differentially expressed marker genes were overlapped and their biological functions were analyzed. Results: Totally, five immune cell subpopulations were annotated in OA synovial tissues including macrophages, dendritic cells, T cells, monocytes and B cells. Pseudo-time analysis revealed the underlying evolution process in the inflammatory microenvironment of OA synovial tissue. There was close crosstalk between five cell types according to the ligand-receptor network. The genetic heterogeneity was investigated between OA and normal synovial tissues. Furthermore, functional annotation analysis showed the intercellular heterogeneity across immune cells in OA synovial tissues. Conclusion: This study offered insights into the heterogeneity of OA, which provided in-depth understanding of the transcriptomic diversities within synovial tissue. This transcriptional heterogeneity may improve our understanding on OA pathogenesis and provide potential molecular therapeutic targets for OA.

Highlights

Osteoarthritis (OA) represents the most frequent ageassociated chronic degenerative joint disease (Maumus et al, 2020)
The gene expression profiles of OA and healthy synovial tissue specimens were obtained from two microarray datasets GSE55235 and GSE55457
With the criteria of False discovery rate (FDR)1.5, 148 genes were up-regulated and 127 genes were down-regulated in OA compared to healthy synovial tissues in the GSE55235 dataset (Figures 1A,B; Supplementary Table S1)

Summary

Introduction

Osteoarthritis (OA) represents the most frequent ageassociated chronic degenerative joint disease (Maumus et al, 2020). Aging is the key driving force in OA (Deng et al, 2019). The incidence of OA in the middle-aged population is 40–80%, and the disability rate is >50% (Zhang et al, 2020b). The pathogenesis of OA involves the entire joint, composed of articular cartilage, synovial membrane as well as subchondral bone (Griffin and Scanzello, 2019). Traditional therapeutic strategies such as non-steroidal anti-inflammatory drugs only ease pain symptoms. There is still a lack of FDA-approved disease-modifying OA drugs that may remiss the pain and restrain joint degradation (Grandi and Bhutani, 2020)

Methods

Results

Discussion

Conclusion