Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2025.008

Transcriptomic analysis reveals distinct molecular signatures and regulatory networks of osteoarthritic chondrocytes versus mesenchymal stem cells during chondrogenesis

Tsung-Yu Lin^{1, 2, 3}, Viraj Krishna Mishra⁴, Rajni Dubey⁵, Thakur Prasad Chaturvedi⁶, Shankar Narayan A⁷, Hsu-Wei Fang³, Lung-Wen Tsai^{8, 9, 10}, Navneet Kumar Dubey^{11, 12}

¹ Department of Orthopedic Surgery, Mackay Memorial Hospital, Taipei City 104, Taiwan

² Mackay Junior College of Medicine, Nursing, and Management, New Taipei City 252, Taiwan

³ Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei 106344, Taiwan

⁴ BioSource Tech, Ambala 133101, Haryana, India

⁵ Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan

⁶ Division of Orthodontics and Dentofacial Orthopaedics, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

⁷ Center of Excellence, Akhand Jyoti Eye Hospital, Mastichak, Patna, Bihar 841219, India

⁸ Department of Medicine Research, Taipei Medical University Hospital, Taipei 11031, Taiwan

⁹ Department of Information Technology Office, Taipei Medical University Hospital, Taipei 11031, Taiwan

¹⁰ Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei 11031, Taiwan

¹¹ Victory Biotechnology Co., Ltd., Taipei 114757, Taiwan

¹² Executive Programme in Healthcare Management, Indian Institute of Management Lucknow 226013, India

Background: Recent regenerative studies imply conflicting results on knee osteoarthritic (OA) chondrocytes and mesenchymal stem cells (MSC)-mediated cartilage constructs in terms of compressive properties and tensile strength. This could be attributed to different gene expression patterns between MSC and OA chondrocytes during chondrogenic differentiation. Therefore, we analyzed differentially expressed genes (DEGs) between OA and MSC-derived chondrocytes using bioinformatics tools.

Methods: We downloaded and analyzed the GSE19664 dataset from the Gene Expression Omnibus to identify DEGs. DAVID was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, while a protein-protein interaction network of DEGs was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) and identified hub genes by CytoHubba.

Results: A total of 43 DEGs identified (15 downregulated and 28 upregulated) were found to be deregulated between OA and MSC-derived chondrocytes. KEGG analysis revealed the enrichment of complement and coagulation cascades and other pathways among the studied chondrocytes. The pathway enrichment identified top KEGG, gene ontology biological process, molecular function, and cellular component. The hub networks identified the top 5 hub genes involved in chondrogenesis, including CLU, PLAT, CP, TIMP3, and SERPINA1.

Conclusions: Our results identified significant genes involved in chondrogenesis. These findings provide new avenues for exploring the genetic mechanism underlying cartilage synthesis and novel targets for preclinical intervention and clinical treatment.

Keywords: osteoarthritis, chondrocytes, mesenchymal stem cells, differentially expressed genes (DEGs), protein-protein interaction (PPI), hub genes, gene ontology (GO)

Received: May 22, 2024; Revised: January 9, 2025; Accepted: March 19, 2025; Prepublished online: April 17, 2025