Cellular Landscape of Synovial Chondromatosis Synovium Revealed by Single-Cell RNA Sequencing

Synovial chondromatosis (SC) is a rare joint disorder characterized by cartilaginous loose bodies, yet its cellular underpinnings remain incompletely understood. To define the cellular landscape in SC, single-cell RNA sequencing was performed on synovial tissue obtained from both healthy individuals and SC patients. Analysis of this comprehensive dataset revealed significant alterations in the cellular composition and unique transcriptional profiles of key synovial cell populations within SC synovium. Specifically, a marked increase in the proportion of distinct fibroblast subpopulations (F3 and F4) engaged in extracellular matrix (ECM) synthesis and degradation was observed. Concurrently, the macrophage compartment exhibited a notable shift towards M2-like and M4-like phenotypes. Furthermore, an expanded and dynamically transitioning proliferative immune cell (ProIC) population was identified, with distinct C0 and C1 subpopulations showing unique functional characteristics and a differentiation trajectory from C0 to C1. Beyond individual cellular characteristics, interrogation of intercellular communication networks revealed potentially enhanced signaling, particularly between fibroblasts and macrophages mediated by FTL-SCARA5 interactions, and between macrophages and ProICs via CD74-MIF/other CD74 ligand interactions. These findings offer a comprehensive and detailed characterization of the cellular heterogeneity and altered cellular states associated with SC. This detailed cellular atlas provides a crucial foundation for future functional studies aimed at dissecting the precise roles of these observed cellular alterations in SC pathogenesis and exploring potential therapeutic targets.