Identification of key regulators responsible for dysregulated networks in osteoarthritis by large-scale expression analysis

• Published in: Journal of orthopaedic surgery and research 2021-04, Vol.16 (1), p.259-259, Article 259
• Main Authors: Shi, Song, Wan, Fuyin, Zhou, Zhenyu, Tao, Ran, Lu, Yue, Zhou, Ming, Liu, Fan, Liu, Yake
• Format: Article
• Language: English
• Subjects: Arthritis; Bone matrix; Cardiac glycosides; Care and treatment; Cartilage; Cartilage diseases; Collagen; Computer applications; Data analysis; Datasets; Drug approval; Drug development; Drug repurposing; Extracellular matrix; FOXO3 protein; Gene expression; Genes; Genetic research; Genomes; Genomics; Glycosides; Health aspects; Homeostasis; Inflammation; Musculoskeletal diseases; Orthopedics; Ossification; Osteoarthritis; Pain; Pathogenesis; Protein interaction; Protein-protein interactions; Proteins; Synovium; Therapeutic applications; Therapeutic targets; Transcriptional profiling; Transcriptomes
• ISSN: 1749-799X; 1749-799X
• DOI: 10.1186/s13018-021-02402-9

Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA. We collected genome-wide transcriptome data performed on 132 OA and 74 normal human cartilage or synovium tissues from 7 independent datasets. Differential gene expression analysis and functional enrichment were performed to identify genes and pathways that were dysregulated in OA. The computational drug repurposing method was used to uncover drugs that could be repurposed to treat OA. We identified several pathways associated with the development of OA, such as extracellular matrix organization, inflammation, bone development, and ossification. By protein-protein interaction (PPI) network analysis, we prioritized several hub genes, such as JUN, CDKN1A, VEGFA, and FOXO3. Moreover, we repurposed several FDA-approved drugs, such as cardiac glycosides, that could be used in the treatment of OA. We proposed that the hub genes we identified would play a role in cartilage homeostasis and could be important diagnostic and therapeutic targets. Drugs such as cardiac glycosides provided new possibilities for the treatment of OA.