Research progress of fibroblast-like synoviocytes in osteoarthritis

WANG Jia-hao; GAO Yan; LI Chong; HAO Yan-ming

doi:10.3969/j.issn.2095-252X.2025.10.012

Abstract：Osteoarthritis (OA) is a common degenerative joint disease that has shown increasing prevalence and a trend toward younger onset in recent years, severely impairing quality of life and imposing a significant socioeconomic burden. Fibroblast-like synoviocytes (FLS) have emerged as critical effector cells in OA due to their central role in maintaining synovial inflammation, promoting joint destruction, and driving subchondral bone remodeling. Although substantial progress has been made in understanding the mechanisms of FLS pathological activation, a comprehensive, structured review and integrative framework is still lacking. In this review, we propose a three-tiered model "Input-Regulation-Output" to systematically summarize the multilevel regulatory network underlying the transition of FLS from a quiescent to a pathological state. The input layer includes extracellular stimuli such as proinflammatory cytokines, chemokines, and damage-associated molecular patterns; the regulatory layer covers gene expression mechanisms mediated by transcription factors and non-coding RNAs; and the output layer focuses on altered protein expression, post-translational modifications, and phenotypic remodeling. Additionally, we integrate recent findings on FLS interactions with macrophages, chondrocytes, and osteoclasts within the OA joint microenvironment to depict a coordinated pathogenic network. By constructing a functional atlas of FLS pathological activation, this review aims to identify key regulatory nodes in OA progression and provide a theoretical basis for the discovery of early diagnostic biomarkers and the development of targeted therapeutic strategies.