Jishizhan Chen1, Lidan Chen1,2, Jia Hua3,4,5, Wenhui Song6. 1. UCL Centre for Biomaterials in Surgical Reconstruction and Regeneration, Division of Surgery & Interventional Science, University College London, London, NW3 2PF, UK. 2. Centre of Maxillofacial Surgery and Digital Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China. 3. UCL Institute of Orthopaedics and Musculoskeletal Science, Division of Surgery & Interventional Science, University College London, Stanmore, London, HA7 4AP, UK. 4. The Griffin Institute (Northwick Park Institute for Medical Research), Harrow, London, HA1 3UJ, UK. 5. Faculty of Science and Technology, Middlesex University, London, NW4 4BT, UK. 6. UCL Centre for Biomaterials in Surgical Reconstruction and Regeneration, Division of Surgery & Interventional Science, University College London, London, NW3 2PF, UK. w.song@ucl.ac.uk.
Abstract
BACKGROUND: Bioengineering has demonstrated the potential of utilising mesenchymal stem cells (MSCs), growth factors, and mechanical stimuli to treat cartilage defects. However, the underlying genes and pathways are largely unclear. This is the first study on screening and identifying the hub genes involved in mechanically enhanced chondrogenesis and their potential molecular mechanisms. METHODS: The datasets were downloaded from the Gene Expression Omnibus (GEO) database and contain six transforming growth factor-beta-3 (TGF-β3) induced bovine bone marrow-derived MSCs specimens and six TGF-β3/dynamic-compression-induced specimens at day 42. Screening differentially expressed genes (DEGs) was performed and then analysed via bioinformatics methods. The Database for Annotation, Visualisation, and Integrated Discovery (DAVID) online analysis was utilised to obtain the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network of the DEGs was constructed based on data from the STRING database and visualised through the Cytoscape software. The functional modules were extracted from the PPI network for further analysis. RESULTS: The top 10 hub genes ranked by their connection degrees were IL6, UBE2C, TOP2A, MCM4, PLK2, SMC2, BMP2, LMO7, TRIM36, and MAPK8. Multiple signalling pathways (including the PI3K-Akt signalling pathway, the toll-like receptor signalling pathway, the TNF signalling pathway, and the MAPK pathway) may impact the sensation, transduction, and reaction of external mechanical stimuli. CONCLUSIONS: This study provides a theoretical finding showing that gene UBE2C, IL6, and MAPK8, and multiple signalling pathways may play pivotal roles in dynamic compression-enhanced chondrogenesis.
BACKGROUND: Bioengineering has demonstrated the potential of utilising mesenchymal stem cells (MSCs), growth factors, and mechanical stimuli to treat cartilage defects. However, the underlying genes and pathways are largely unclear. This is the first study on screening and identifying the hub genes involved in mechanically enhanced chondrogenesis and their potential molecular mechanisms. METHODS: The datasets were downloaded from the Gene Expression Omnibus (GEO) database and contain six transforming growth factor-beta-3 (TGF-β3) induced bovine bone marrow-derived MSCs specimens and six TGF-β3/dynamic-compression-induced specimens at day 42. Screening differentially expressed genes (DEGs) was performed and then analysed via bioinformatics methods. The Database for Annotation, Visualisation, and Integrated Discovery (DAVID) online analysis was utilised to obtain the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network of the DEGs was constructed based on data from the STRING database and visualised through the Cytoscape software. The functional modules were extracted from the PPI network for further analysis. RESULTS: The top 10 hub genes ranked by their connection degrees were IL6, UBE2C, TOP2A, MCM4, PLK2, SMC2, BMP2, LMO7, TRIM36, and MAPK8. Multiple signalling pathways (including the PI3K-Akt signalling pathway, the toll-like receptor signalling pathway, the TNF signalling pathway, and the MAPK pathway) may impact the sensation, transduction, and reaction of external mechanical stimuli. CONCLUSIONS: This study provides a theoretical finding showing that gene UBE2C, IL6, and MAPK8, and multiple signalling pathways may play pivotal roles in dynamic compression-enhanced chondrogenesis.
Authors: Liesbet Geris; Katleen Vandamme; Ignace Naert; Jos Vander Sloten; Hans Van Oosterwyck; Joke Duyck Journal: Tissue Eng Part A Date: 2010-07-27 Impact factor: 3.845