Distinct subsets of synovial fibroblasts control cartilage destruction in joint diseases

Inflammation-induced bone destruction is the main cause of progressive joint damage in rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, depending on the tissue microenvironment stimulators, the synovium transforms into a hyperplastic invasive tissue. The synovium includes two specific subsets of fibroblasts surrounding the joints: lining and sublining synovial fibroblasts (SFs). These SFs grow and interact with immune cells invading the bone and cartilage; specifically, SFs, which are the major mesenchymal cells in the joints, develop an aggressive phenotype, thereby producing cytokines and proteases involved in arthritis pathogeneses. Transcriptomic differences in the heterogeneity of SFs reflect the joint-specific origins of the SFs interacting with immune cells. To understand the subsets of SFs that lead to joint damage in arthritis, clarifying the distinct phenotypes and properties of SFs and understanding how they influence bone cells, such as osteoclasts and chondrocytes, is crucial. This review provides an overview of the advancements in the understanding of SF subsets and features, which may aid in identifying newer therapeutic targets.