Single-cell and bulk tissue sequencing unravels the heterogeneity of synovial microenvironment in arthrofibrosis.

Arthrofibrosis (AF) is a debilitating complication that occurs after trauma or surgery, leading to functional impairment and surgical failures worldwide. This study aimed to uncover the underlying mechanism of AF. A total of 141 patients were enrolled, and synovial samples were collected from both patients and animal models at different time points. Single-cell RNA-sequencing (scRNA-seq) and bulk tissue RNA sequencing (bulk-seq) were employed to profile the distinct synovial microenvironment. This study revealed changes in cell proportions during AF pathogenesis and identified Engrailed-1 (EN1) as a key transcription factor strongly associated with disease severity and clinical prognosis. Additionally, the researchers discovered a specific type of synovial fibroblast called DKK3-SLF, which played a critical role in driving AF development. These findings shed light on the composition and heterogeneity of the synovial microenvironment in AF, offering potential avenues for identifying therapeutic targets and developing clinical treatments for AF and other fibrotic diseases.