Các mạch tương tác trung gian miRNA dự đoán thiếu oxy và ức chế quá trình tạo xương của tế bào gốc, cùng với việc điều hòa không ổn định angiogenesis liên quan đến hoại tử vô mạch đầu xương đùi

International Orthopaedics - Tập 42 - Trang 1605-1614 - 2018
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 Yip4, Mel S. Lee1
1Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
3Department of Orthopedic Surgery, Eda Hospital, Kaohsiung, Taiwan
4Division of Cardiology, Department of Internal Medicine, Kaohisung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
5Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan

Tóm tắt

MicroRNA (miRNA) liên quan đến nhiều tình trạng bệnh lý khác nhau và có thể phục vụ như một dấu ấn sinh học chẩn đoán hoặc điều trị. Nghiên cứu này đã cố gắng xác định các miRNA được biểu hiện khác nhau để dự đoán các cơ chế bệnh sinh có thể liên quan đến hoại tử vô mạch đầu xương đùi (ONFH). Chúng tôi đã so sánh các miRNA trong máu ngoại vi của 46 bệnh nhân mắc ONFH và 85 đối chứng khỏe mạnh bằng cách sử dụng phương pháp microarray và phản ứng chuỗi polymerase kỹ thuật số giọt (ddPCR). Các mạng lưới tương tác giả định giữa các miRNA có phản ứng khác nhau đã được phân tích bằng các công cụ dự đoán sinh bioinformatics dựa trên web. Phương pháp microarray đã xác định được 51 miRNA thể hiện khác nhau với ít nhất thay đổi gấp đôi (tăng cường biểu hiện ở 34 miRNA và giảm biểu hiện ở 17 miRNA), và kết quả đã được xác nhận bằng ddPCR với sáu miRNA đã chọn. Phân tích mạng lưới gen bioinformatics tập trung vào sáu miRNA đã phát hiện miR-18a và miR-19a tăng cường liên quan đến quá trình tạo mạch sau khi gây thiếu máu; miR-138-1 tăng cường có thể ức chế sự biệt hóa tế bào tạo xương của các tế bào gốc trung mô; các gen mục tiêu nhiều nhất, p53 và SERBP1, liên quan đến thiếu oxy và giảm phân hủy fibrin. Nghiên cứu này kết hợp phân tích miRNA với bioinformatics và dự đoán rằng thiếu oxy, ức chế quá trình tạo xương của tế bào gốc, và angiogenesis điều hòa không ổn định có thể được phối hợp thông qua các mạch tương tác miRNA trong sinh bệnh học của ONFH.

Từ khóa

#miRNA #hoại tử vô mạch #tạo xương #tế bào gốc #thiếu oxy #angiogenesis

Tài liệu tham khảo

Chen CC, Lin CL, Chen WC, Shih HN, Ueng SWN, Lee MS (2009) Vascularized iliac bone-grafting for osteonecrosis with segmental collapse of the femoral head. J Bone Joint Surg Am 91A:2390–2394 Lee MS, Hsieh PH, Shih CH, Wang CJ (2010) Nontraumatic osteonecrosis of the femoral head—from clinical to bench. Chang Gung Med J 33:351–310 Wang Y, Li Y, Mao K, Li J, Cui Q, Wang GJ (2003) Alcohol-induced adipogenesis in bone and marrow: a possible mechanism for osteonecrosis. Clin Orthop Relat Res 410:213–224 Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P (1997) Thrombophilia and hypofibrinolysis: Pathoetiologies of osteonecrosis. Clin Orthop Relat Res 334:43-56 Glueck CJ, Fontaine RN, Gruppo R, Stroop D, Sieve-Smith L, Tracy T, Wang P (1999) The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin Orthop Relat Res 366:133–146 Björkman A, Svensson PJ, Hillarp A, Burtscher IM, Rünow A (2004) Factor V Leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res 425:168–172 Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ (2006) Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J Orthop Res 24:1722–1728 Clueck CJ, Freiberg RA, Oghene J, Fontaine RN, Wang P (2007) Association between the T-786C eNOS polymorphism and idiopathic osteonecrosis of the head of the femur. J Bone Joint Surg Am 89(A):2460–2468 Peng KT, Huang KC, Huang TW, Lee YS, Hsu WH, Hsu RW, Ueng SW, Lee MS (2014) Single nucleotide polymorphisms other than factor V Leiden are associated with coagulopathy and osteonecrosis of the femoral head in Chinese patients. PLoS One 9(8):e104461. https://doi.org/10.1371/journal.pone.0104461 Lu ML, Sung PH, Huang TW, Chen SC, Lin R, Yip HK, Lee MS (2017) Risks of factor V rs6020 or methylenetetrahydrofolate reductase rs12121543 polymorphism with hyperhomocysteinemia in the development of osteonecrosis of the femoral head. J Hip Surg 1:61–65 Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826 Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297 Kloosterman WP, Plasterk RH (2006) The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450 Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105:10513–10518 Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, Hood LE, Galas DJ (2009) Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A 106:4402–4407 Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani K, Ito H, Nakamura T (2010) Plasma and synovial fluid micro RNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 12:R86,1–R8614 Waldman SA, Terzic A (2008) MicroRNA signatures as diagnostic and therapeutic targets. Clin Chem 54:943–944 Yuan H, Von Roemeling C, Gao H, Zhang J, Guo G, Yan Z (2015) Analysis of altered microRNA expression profile in the reparative interface of the femoral head with osteonecrosis. Exp Mol Pathol 98:158–163 Bian Y, Qian W, Lin H, Zhao RC, Shan WX, Weng X (2015) Pathogenesis of glucocorticoid-induced avascular necrosis: a microarray analysis of gene expression in vitro. Int J Mol Med 36:678–684 Hao C, Yang S, Xu W, Shen JK, Ye S, Liu X, Dong Z, Xiao B, Feng Y (2016) MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3. Sci Rep 6:22599. https://doi.org/10.1038/srep22599 Chen L, HolmstrØm K, Qiu W, Ditzel N, Shi K, Hokland L, Kassem M (2004) MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem. Cell 32:902–912 Wang T, Teng S, Zhang Y, Wang F, Ding H, Guo L (2017) Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head. Exp Ther Med 13:669–675 Zhao J, Wu Z, Wang L, Feng D, Cheng L (2016) MicroRNA-145 mediates steroid-induced necrosis of the femoral head by targeting the OPG/RANK/RANKL signaling pathway. PLoS One 11(7):e0159805. https://doi.org/10.1371/journal.pone.0159805 Huang G, Wei Y, Zhao G, Xia J, Wang S, Wu J, Chen F, Chen J, Shi J (2017) Microarray-based screening of differentially expressed genes in glucocorticoid-induced avascular necrosis. Mol Med Rep 15:3583–3590 Gardeniers JWM (1993) Report of the committee of staging and nomenclature. ARCO. Newsletter 5:79–82 Sales G, Coppe A, Bisognin a B, Bortoluzzi S, Romualdi C (2010) MAGIA, a web-based tool for miRNA and genes integrated analysis. Nucleic Acids Res 38:W352–W359. https://doi.org/10.1093/nar/gkq423 Yoo JK, Park CH, Ha YC, Lee YK, Koo KY (2016) Ischemic diseases of the hip; osteonecrosis, borderline necrosis and bone marrow edema syndrome. Formosan J Musculoskel Disord 7:145–152. https://doi.org/10.6492/FJMD.20151215 Lian JB, Stein GS, van Wijnen AJ, Stein JL, Hassan MQ, Gaur T, Zhang Y (2013) MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol 8:212–227 Wu RW, Wang FS, Ko JY, Wang CJ, Wu SL (2008) Comparative serum proteome expression of osteonecrosis of the femoral head in adults. Bone 43:561–566 Wang J, Guan X, Guo F, Zhou J, Chang A, Sun B, Cai Y, Ma Z, Dai C, Li X, Wang B (2013) miR-30e reciprocally regulates the differentiation of adipocytes and osteoblasts by directly targeting low-density lipoprotein receptor-related protein 6. Cell Death Dis 4:e845. https://doi.org/10.1038/cddis.2013.356 Wu T, Zhou H, Hong Y, Li J, Jiang X, Huang H (2012) miR-30 family members negatively regulate osteoblast differentiation. J Biol Chem 287:7503–7511 Tomé M, López-Romero P, Albo C, Sepúlveda JC, Fernández-Gutiérrez B, Dopazo A, Bernad A, Bonzález MA (2011) miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ 18:985–995 Bonauer A, Dimmeler S (2009) The microRNA-17-92 cluster: still a miracle? Cell Cycle 8:3866–3873 He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM (2005) A microRNA polycistron as a potential human oncogene. Nature 435:828–833 Tréguer K, Heinrich EM, Ohtani K, Bonauer A, Dimmeler S (2012) Role of the microRNA-17-92 cluster in the endothelial differentiation of stem cells. J Vasc Res 49:447–460 Gao Y, Qian J, Chen Z, Fu M, Xu J, Xia Y, Ding X, Yang X, Cao Y, Zou Y, Ren J, Sun A, Ge J (2016) Suppression of Bim by microRNA-19a may protect cardiomyocytes against hypoxia-induced cell death via autophagy activation. Toxicol Lett 257:72–83. https://doi.org/10.1016/j.toxlet.2016.05.019 Eskildsen T, Taipaleenmäki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, Bak M, Kauppinen S, Kassem M (2011) MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. PNAS 108:6139–6144. https://doi.org/10.1073/pnas.1016758108 Qu B, Xia X, Wu HH, Tu CQ, Pan XM (2014) PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells. Biochem Biophy Res Commun 448:241–247. https://doi.org/10.1016/j.bbrc.2014.04.091 Fiedle J, Stöhr A, Gupta SK, Hartmann D, Holzmann A, Just A, Hansen A, Kilfiker-Kleiner D, Eschenhagen T, Thum T (2014) Functional microRNA library screening identifies the hypoxamir miR-24 as a potent regulator of smooth muscle cell proliferation and vascularization. Antioxid Redox Signal 21:1167–1176. https://doi.org/10.1089/ars.2013.5418 Meloni M, Marchetti M, Garner K, Littlejohns B, Sala-Newby G, Xenophontos N, Floris I, Suleiman M, Madeddu P, Caporali A, Emanueli C (2013) Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. Mol Ther 21:1390–1402. https://doi.org/10.1038/mt.2013.89 Wu J, Ji X, Zhu L, Jiang Q, Wen Z, Xu S, Shao W, Cai J, Du Q, Zhu Y, Mao J (2013) Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming of colon cancer cells. Cancer Lett 329:155–163. https://doi.org/10.1016/j.canlet.2012.10.038 Mao Y, Shen J, Lu Y, Lin K, Wang H, Li Y, Chang P, Walker MG, Li D (2017) RNA sequencing analyses reveal novel differentially expressed genes and pathways in pancreatic cancer. Oncotarget 8:42537–42547. https://doi.org/10.18632/oncotarget.16451 Das B, Bayat-Mhkhtari R, Tsui M, Lotfi S, Tsuchida R, Felsher DW, Yeger H (2012) HIF-2α suppressses p53 to enhance the stemness and regenerative potential of human embryonic stem cells. Stem Cells 30:1685–1695 Teodoro JG, Evans SK, Green MR (2007) Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. J Mol Med 85:1175–1186