Gour-Shenq Kao1,2, Yuan-Kun Tu3, Pei-Hsun Sung4, Feng-Sheng Wang2,5, Yu-Der Lu1, Chen-Ta Wu1, Rio L C Lin1,2, Hon-Kan Yip6, Mel S Lee7. 1. Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan. 2. Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan. 3. Department of Orthopedic Surgery, Eda Hospital, Kaohsiung, Taiwan. 4. Division of Cardiology, Department of Internal Medicine, Kaohisung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan. 5. Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan. 6. Division of Cardiology, Department of Internal Medicine, Kaohisung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan. han-gung@msa.hinet.net. 7. Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan. bone@doctor.com.
Abstract
PURPOSE: MicroRNAs (miRNAs) are associated with various pathologic conditions and can serve as diagnostic or therapeutic biomarkers. This study tried to identify the differentially expressed miRNAs to predict the possible pathomechanisms involved in osteonecrosis of the femoral head (ONFH). METHODS: We compared the peripheral blood miRNAs in 46 patients with ONFH and 85 healthy controls by microarray and droplet digital polymerase chain reaction (ddPCR). Putative interacted networks between the differentially responded miRNAs were analyzed by web-based bioinformatics prediction tools. RESULTS: Microarray identified 51 differentially expressed miRNAs with at least twofold change (upregulation in 34 and downregulation in 17), and the results were validated by ddPCR using six selected miRNAs. Bioinformatics genetic network analysis focusing on the six miRNAs found the upregulated miR-18a and miR-19a are associated with angiogenesis after induction of ischemia; the upregulated miR-138-1 can inhibit osteogenic differentiation of mesenchymal stem cells; the most targeted genes, p53 and SERBP1, are associated with hypoxia and hypofibrinolysis. CONCLUSIONS: This study combined the miRNA analysis with the bioinformatics and predicts that hypoxia, inhibited osteogenesis of stem cells, and dysregulated angiogenesis might be orchestrated through the miRNA interacting circuits in the pathogenesis of ONFH.
PURPOSE: MicroRNAs (miRNAs) are associated with various pathologic conditions and can serve as diagnostic or therapeutic biomarkers. This study tried to identify the differentially expressed miRNAs to predict the possible pathomechanisms involved in osteonecrosis of the femoral head (ONFH). METHODS: We compared the peripheral blood miRNAs in 46 patients with ONFH and 85 healthy controls by microarray and droplet digital polymerase chain reaction (ddPCR). Putative interacted networks between the differentially responded miRNAs were analyzed by web-based bioinformatics prediction tools. RESULTS: Microarray identified 51 differentially expressed miRNAs with at least twofold change (upregulation in 34 and downregulation in 17), and the results were validated by ddPCR using six selected miRNAs. Bioinformatics genetic network analysis focusing on the six miRNAs found the upregulated miR-18a and miR-19a are associated with angiogenesis after induction of ischemia; the upregulated miR-138-1 can inhibit osteogenic differentiation of mesenchymal stem cells; the most targeted genes, p53 and SERBP1, are associated with hypoxia and hypofibrinolysis. CONCLUSIONS: This study combined the miRNA analysis with the bioinformatics and predicts that hypoxia, inhibited osteogenesis of stem cells, and dysregulated angiogenesis might be orchestrated through the miRNA interacting circuits in the pathogenesis of ONFH.
Authors: Lin He; J Michael Thomson; Michael T Hemann; Eva Hernando-Monge; David Mu; Summer Goodson; Scott Powers; Carlos Cordon-Cardo; Scott W Lowe; Gregory J Hannon; Scott M Hammond Journal: Nature Date: 2005-06-09 Impact factor: 49.962