Abstract

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic disorders that primarily involve joints. The inflammation of the synovium can be observed in both of the two diseases. Synovial fibroblasts (SFs) play an important role in the inflammatory process of the synovium. The functional states of synovial fibroblasts are heterogeneous, and the detailed transition process of their functional states is still unclear. By using transcriptomic data of SFs at a single-cell level, we found a similar transition process for SFs in RA and OA. We also identified the potential regulatory effects of the WNT signaling pathway, the TGF-β signaling pathway, the FcεRI signaling pathway, and the ERBB signaling pathway on modifying the SFs' functional state. These findings indicate potentially overlapped pathogenic mechanisms in these two diseases, which may help uncover new therapeutic targets to ameliorate disease progression.

Highlights

  • Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic disorders that primarily involve joints

  • OA has long been viewed as a degenerative disease of the cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis [2]

  • Five states can be identified with Monocle (Figure 2(b)), and Synovial fibroblasts (SFs) from RA and OA showed a similar pattern of developmental trajectory (Figure 2(c))

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Summary

Introduction

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic disorders that primarily involve joints. OA has long been viewed as a degenerative disease of the cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis [2]. The synovium consists of the synovial lining and the subjacent vascular and areolar tissue up to the capsule. Synovial fibroblasts (SFs) are dominant cells in normal synovium [3]. Insights into the transition process of synovial fibroblasts can help us better understand the pathophysiological role of SFs in both RA and OA. No study has explored the transitional process of the synovial fibroblasts of these 2 diseases in vivo in humans. By using the single-cell RNA-sequencing data of RA and OA synovial fibroblasts (Figure 1), we aim to explore the potential transition process of SFs in vivo and elucidate their corresponding functional states

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