Exploring the molecular mechanisms and shared potential drugs between rheumatoid arthritis and arthrofibrosis based on large language model and synovial microenvironment analysis

• Published in: Scientific reports 2024-08, Vol.14 (1), p.18939-14
• Main Authors: Wei, Zhaoquan, Chen, Xi, Sun, Youshi, Zhang, Yifei, Dong, Ruifang, Wang, Xiaojing, Chen, Shuangtao
• Format: Article
• Language: English
• Subjects: 692/4023/1670/498; 692/699/1670/122; Arthritis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Arthrofibrosis; Autoimmune diseases; CD34 antigen; Cellular Microenvironment - drug effects; Correlation analysis; Data Mining; Drug development; Drug Repositioning; Drug screening; Drugs; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Humanities and Social Sciences; Humans; Hyperplasia; Joint diseases; Microenvironments; Molecular modelling; multidisciplinary; Osteoarthritis; Pathogenesis; Psoriatic arthritis; Rheumatoid arthritis; Science; Science (multidisciplinary); Sublining fibroblasts; Synovial Membrane - metabolism; Synovial Membrane - pathology; Synovial microenvironment; Therapeutic targets
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-69080-5

Rheumatoid arthritis (RA) and arthrofibrosis (AF) are both chronic synovial hyperplasia diseases that result in joint stiffness and contractures. They shared similar symptoms and many common features in pathogenesis. Our study aims to perform a comprehensive analysis between RA and AF and identify novel drugs for clinical use. Based on the text mining approaches, we performed a correlation analysis of 12 common joint diseases including arthrofibrosis, gouty arthritis, infectious arthritis, juvenile idiopathic arthritis, osteoarthritis, post infectious arthropathies, post traumatic osteoarthritis, psoriatic arthritis, reactive arthritis, rheumatoid arthritis, septic arthritis, and transient arthritis. 5 bulk sequencing datasets and 4 single-cell sequencing datasets of RA and AF were integrated and analyzed. A novel drug repositioning method was found for drug screening, and text mining approaches were used to verify the identified drugs. RA and AF performed the highest gene similarity (0.77) and functional ontology similarity (0.84) among all 12 joint diseases. We figured out that they share the same key pathogenic cell including CD34 + sublining fibroblasts (CD34-SLF) and DKK3 + sublining fibroblasts (DKK3-SLF). Potential therapeutic target database (PTTD) was established with the differential expressed genes (DEGs) of these key pathogenic cells. Based on the PTTD, 15 potential drugs for AF and 16 potential drugs for RA were identified. This work provides a new perspective on AF and RA study which enhances our understanding of their pathogenesis. It also shed light on their underlying mechanism and open new avenues for drug repositioning studies.