郇松玮;査振刚;王华军;刘宁;

• 1:暨南大学骨科疾病研究所暨南大学附属第一医院骨关节与运动医学中心

摘要(Abstract)：

[目的]分析膝骨关节炎小鼠模型中软骨及软骨下骨中MicroRNA-214(miR-214)的表达。[方法]对正常小鼠与miR-214敲除鼠采用切断小鼠的前交叉韧带与切除内侧半月板的方法建立膝骨关节模型,分别处理2、4、6周后,取小鼠软骨及软骨下骨行组织学Mankin评分,应用实时荧光定量PCR方法检测miR-214的表达以及基于Micro-CT观察软骨下骨的变化。[结果] miR-214在正常小鼠的各组软骨与软骨下骨中均有表达。而且4组不同处理时间的正常小鼠的骨关节炎严重程度经改良的Mnakin评分差异有统计学意义,同时发现4组软骨中miR-214的表达差异有统计学意义(P<0.05),并且呈现逐渐升高的趋势;骨关节炎发展的严重程度与miR-214的表达水平密切相关。C57小鼠假手术组(A1组)、2周手术组(B1组)、以及4周手术组(C1组)软骨下骨中miR-214表达呈逐渐升高趋势(P<0.05),而且发现手术处理6周组(D1组)中软骨下骨中miR-214的表达量相对于4周(C1组)的骨关节炎组小鼠表达稍下降。miR-214敲除鼠不同手术时间各组2周手术组(B2组)、4周手术组(C2组)、6周手术组(D2组)相对应的正常小鼠手术时间各组(B1、C1与D1)进行对比,发现改良的Mankin评分明显低于后者。同时micro-CT表明miR-214敲除鼠各组结果相对好于正常小鼠手术各组。[结论] miR-214的表达水平与骨性关节炎发展的严重程度密切相关,表明miR-214可能与关节软骨、特别是骨性关节炎的发生、发展有密切联系。

关键词(KeyWords)： 骨关节炎;小鼠模型;软骨;软骨下骨;MicroRNA

Abstract:

Keywords:

基金项目(Foundation): 广东省医学科学技术研究基金项目(编号:A2016502)

作者(Author): 郇松玮;査振刚;王华军;刘宁;

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DOI:

参考文献(References)：

• [1]Cross M,Smith E,Hoy D,et al.The global burden of hip and knee osteoarthritis:estimates from the global burden of disease 2010study.Annals of the rheumatic diseases[J].Annrheumdis,2014,13:763.
• [2]Mosher TJ,Zhang Z,Reddy R,et al.Knee articular cartilage damage in osteoarthritis:analysis of MR image biomarker reproducibility in ACRIN-PA 4001 multicenter trial[J].Radiology,2011,258(3):832-842.
• [3]Goldring MB,Goldring SR.Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis[J].Annals of the New York Acad Sci,2010,1192(1):230-237.
• [4]Lu M,Zhang Q,Deng M,et al.An analysis of human microRNAand disease associations[J].PloS One,2008,3(10):e3420.
• [5]Miyaki S,Asahara H.Macro view of microRNA function in osteoarthritis[J].Nat Rev Rheumatol,2012,8(9):543.
• [6]Lian JB,Stein GS,Van Wijnen AJ,et al.MicroRNA control of bone formation and homeostasis[J].Nat Rev Endocrinol,2012,8(4):212.
• [7]Thum T,Gross C,Fiedler J,et al.MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts[J].Nature,2008,456(7224):980.
• [8]Yamasaki K,Nakasa T,Miyaki S,et al.Expression of microRNA146a in osteoarthritis cartilage[J].Arthritis Rheumatol,2009,60(4):1035-1041.
• [9]Kung L,Zaki S,Ravi V,et al.Utility of circulating serum miRNAs as biomarkers of early cartilage degeneration in animal models of post-traumatic osteoarthritis and inflammatory arthritis[J].Osteoarthritis Cartilage,2017,25(3):426-434
• [10]Yu XM,Meng HY,Yuan XL,et al.MicroRNAs’involvement in osteoarthritis and the prospects for treatments[J].Evid Based Complement Altern Med,2015,2015:1-10.
• [11]Li H,Li T,Fan J,et al.miR-216a rescues dexamethasone suppression of osteogenesis,promotes osteoblast differentiation and enhances bone formation,by regulating c-Cbl-mediated PI3K/AKTpathway[J].Cell Death Differentiation,2015,22(12):1935.
• [12]Mankin HJ,Dorfman H,Lippiello L,et al.Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips.II.Correlation of morphology with biochemical and metabolic data[J].J Bone Joint Surg Am,1971 53(3),523-537.
• [13]He Y,Gram A,Simonsen O,et al.AB0104 develop and evaluate a new modified mankin score system with special attention to subchondral bone[J].Ann Rheumatic Dis,2014 73(Suppl 2):838-838.
• [14]Zhang HT,Yang J,Zha ZG,et al.Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis[J].J Cellular Biochem,2017 118(12):4575-4597.
• [15]Bertuglia A,Lacourt M,Girard C,et al.Osteoclasts are recruited to the subchondral bone in naturally occurring post-traumatic equine carpal osteoarthritis and may contribute to cartilage degradation[J].Osteoarthritis Cartilage,2016,24(3):555-566.
• [16]Shi H,Xu J,Zhang G,et al.Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes[J].BMC,2013,7(1):101.
• [17]Iliopoulos D,Malizos KN,Oikonomou P,et al.Integrative microR-NA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks[J].PloS One,2008,3(11):e3740.
• [18]Wang X,Guo B,Li Q,et al.miR-214 targets ATF4 to inhibit bone formation[J].Nature Med,2013,19(1):93.