Single‐cell RNA sequencing in osteoarthritis

Abstract

Osteoarthritis is a progressive and heterogeneous joint disease with complex pathogenesis. The various phenotypes associated with each patient suggest that better subgrouping of tissues associated with genotypes in different phases of osteoarthritis may provide new insights into the onset and progression of the disease. Recently, single‐cell RNA sequencing was used to describe osteoarthritis pathogenesis on a high‐resolution view surpassing traditional technologies. Herein, this review summarizes the microstructural changes in articular cartilage, meniscus, synovium and subchondral bone that are mainly due to crosstalk amongst chondrocytes, osteoblasts, fibroblasts and endothelial cells during osteoarthritis progression. Next, we focus on the promising targets discovered by single‐cell RNA sequencing and its potential applications in target drugs and tissue engineering. Additionally, the limited amount of research on the evaluation of bone‐related biomaterials is reviewed. Based on the pre‐clinical findings, we elaborate on the potential clinical values of single‐cell RNA sequencing for the therapeutic strategies of osteoarthritis. Finally, a perspective on the future development of patient‐centred medicine for osteoarthritis therapy combining other single‐cell multi‐omics technologies is discussed. This review will provide new insights into osteoarthritis pathogenesis on a cellular level and the field of applications of single‐cell RNA sequencing in personalized therapeutics for osteoarthritis in the future.

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium

“…Recent advancements in single-cell analysis have uncovered diverse synovial fibroblast subsets in both OA and RA synovium. Single-cell RNA-seq data have categorized these subsets into distinct populations, with subsets emerging as a major player in the inflammatory regulatory signaling pathway of OA [5,13,[23][24][25]. A previous study using single-cell RNA-Seq data reported that fibroblast-expressing COLLAGEN, Thy-1, thrombospondin (THBS), and CD34 were major inflammatory subsets in OA [13].…”

“…Recent research has expanded our understanding of OA, revealing intricate interactions among various cell types, and signaling pathways that extend beyond the joint's articular surfaces [5,6]. Central to maintaining joint health are synovial fibroblasts, particularly CD55+ fibroblasts residing in the lining layer of the synovium [7][8][9][10].…”

Signalling interaction between β‐catenin and other signalling molecules during osteoarthritis development

“…Great effort has been devoted to evaluate OA pathogenesis, and contributions of varieties of intrinsic signalling pathways in joint degeneration have been identified such as Wnt/β‐catenin, Indian Hedgehog (Ihh), transforming growth factor β (TGF‐β), epidermal growth factor receptor (EGFR), bone morphogenic protein (BMP), fibroblast growth factor (FGF), nuclear factor κB (NF‐κB), and Runt‐related transcription factor 2 (Runx2), HIF, and Notch. 14 , 15 , 16 , 17 However, effective drugs targeting a specific pathway to halt cartilage degradation has not been generated. Patients with OA finally receive joint replacement surgery after suffering from joint pain and stiffness for long time, highlighting the importance and urging need of finding new effective strategies for OA treatment.…”

Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation

“…Consistent with previous reports, the classical pathways of chondrogenesis, such as transforming growth factor-b (TGF-b) signaling pathway, Wnt signaling pathway, and Hippo signaling pathway, produced significant differences in the differentiation of MSCs to chondrocytes. [42][43][44] After the addition of CyA, the number of differentiated genes reached 9214 for MSC chondrogenesis (Fig. S6, ESI †).…”