[1]陈洪涛,何 云,刘 旭,等.微小RNA-29b-3p通过靶向糖原合酶激酶3β抑制骨髓间充质干细胞成骨分化实验研究[J].陕西医学杂志,2023,52(6):750-755,767.[doi:DOI:10.3969/j.issn.1000-7377.2023.06.025]
　CHEN Hongtao,HE Yun,LIU Xu,et al.MicroRNA-29b-3p inhibits osteogenic differentiation of BMSCs by targeting glycogen synthase kinase 3β[J].,2023,52(6):750-755,767.[doi:DOI:10.3969/j.issn.1000-7377.2023.06.025]
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微小RNA-29b-3p通过靶向糖原合酶激酶3β抑制骨髓间充质干细胞成骨分化实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年6期
页码:
750-755,767
栏目:
临床病理
出版日期:
2023-06-05

文章信息/Info

Title:
MicroRNA-29b-3p inhibits osteogenic differentiation of BMSCs by targeting glycogen synthase kinase 3β
作者:
陈洪涛1; 何 云1; 刘 旭1; 伊力亚尔·阿不都斯木1; 阿布都萨拉木·阿布都克力木1; 伊力哈木·托合提2; 王海龙2
(1.新疆医科大学第六附属医院运动损伤科,新疆 乌鲁木齐 830010; 2.新疆医科大学第七附属医院骨科,新疆 乌鲁木齐 830054)
Author(s):
CHEN Hongtao; HE Yun; LIU Xu; ABUDUSIMU Yiliyaer; ABUDUKELIMU Abudusalamu; TUOHETI Elihamu; WANG Hailong
(Department of Sports Injury,the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830010,China)
关键词:
骨关节炎;  微小RNA-29b-3p;  骨髓间充质干细胞;  成骨分化;  糖原合酶激酶3β
Keywords:
Osteoarthritis;  miR-29b-3p;  Bone marrow mesenchymal stem cells;  Osteogenic differentiation;  Glycogen synthase kinase 3β
分类号:
R 684.3
DOI:
DOI:10.3969/j.issn.1000-7377.2023.06.025
文献标志码:
A
摘要:
目的:探讨微小RNA-29b-3p(miR-29b-3p)在骨关节炎(OA)患者中的表达及其对骨髓间充质干细胞(BMSCs)成骨分化的作用。方法:收集轻度、中度、重度OA患者(各12例)和关节镜膝关节交叉韧带重建患者(对照组,12例)BMSCs,检测miR-29b-3p的表达情况。培养OA患者的BMSCs,通过碱性磷酸酶(ALP)和茜素红S(ARS)染色、实时定量PCR(qRT-PCR)和蛋白免疫印迹检测转染miR-29b-3p mimics、miR-29b-3p inhibitors、糖原合酶激酶3β(GSK3β)过表达载体后成骨分化能力以及相关蛋白和基因的表达情况。结果:与对照组比较,不同严重程度OA患者中miR-29b-3p表达量显著上调,且中度和重度OA患者miR-29b-3p表达量显著高于轻度OA患者(均P<0.01)。BMSCs成骨诱导后,钙浓度和ALP活性均升高,miR-29b-3p表达水平以时间依赖性方式下调。miR-29b-3p过表达后,ALP、Runx家族转录因子2(Runx2)、胶原蛋白1(Col-1)、骨钙素(OCN)均下降。GSK3β在BMSCs诱导骨分化过程中的蛋白水平上调。过表达GSK3β可以部分逆转miR-29b-3p对ALP、Runx2、Col-1和OCN蛋白水平的抑制。结论:miR-29b-3p靶向GSK3β表达抑制BMSCs成骨分化。miR-29b-3p可能成为OA患者治疗的靶标基因。
Abstract:
Objective:To investigate the expression of microRNA-29b-3p(miR-29b-3p)in patients with osteoarthritis(OA)and its effect on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods:BMSCs were collected from 12 patients with mild,moderate,and severe OA,as well as patients with arthroscopic knee cruciate ligament reconstruction(control group,12 cases).and the expression of miR-29b-3p was detected.BMSCs from OA patients were cultured,and alkaline phosphatase(ALP)and alizarin red S(ARS)staining,qRT-PCR and Western blot were used to detect osteogenic differentiation ability and the expression of related proteins and genes were detected after transfection of miR-29b-3p mimics,miR-29b-3p inhibitors and glycogen synthase kinase 3β(GSK3β)overexpression vectors.Results:Compared with the control group,the expression of miR-29b-3p was significantly up-regulated in patients with different severity of OA,and the expression of miR-29b-3p in moderate and severe OA patients was significantly higher than that in mild OA patients(all P<0.01).After osteogenic induction of BMSCs,calcium concentration and ALP activity were increased,and the expression level of miR-29b-3p was down-regulated in a time-dependent manner.After miR-29b-3p overexpression,ALP,Runx2,Col-1 and OCN all decreased.The protein level of GSK3β was up-regulated during BMSCs induced osteogenic differentiation. Overexpression of GSK3β can partially reverse the inhibition of ALP,Runx2,Col-1 and OCN protein levels induced by miR-29b-3p.Conclusion:MiR-29b-3p inhibits the osteogenic differentiation of BMSCs through the GSK3β expression.MiR-29b-3p may become a target gene for the treatment of OA.

参考文献/References:

[1] Tardif G,Pare F,Gotti C,et al.Mass spectrometry-based proteomics identify novel serum osteoarthritis biomarkers[J].Arthritis Res Ther,2022,24(1):120.
[2] 张 帆,周胜利,周奕璇.膝骨关节炎中医外治研究进展[J].陕西中医,2022,43(6):814-817.
[3] Butterfield NC,Curry KF,Steinberg J,et al.Accelerating functional gene discovery in osteoarthritis[J].Nat Commun,2021,12(1):467.
[4] Katsoula G,Kreitmaier P,Zeggini E.Insights into the molecular landscape of osteoarthritis in human tissues[J].Curr Opin Rheumatol,2022,34(1):79-90.
[5] Bonakdari H,Pelletier JP,Abram F,et al.A machine learning model to predict knee osteoarthritis cartilage volume changes over time using baseline bone curvature[J].Biomedicines,2022,10(6):1247.
[6] Yu H,Huang T,Lu WW,et al.Osteoarthritis pain[J].Int J Mol Sci,2022,23(9):4642.
[7] Wang Y,Fan X,Xing L,et al.Wnt signaling:A promising target for osteoarthritis therapy[J].Cell Commun Signal,2019,17(1):97.
[8] Zheng F,Zhang F,Wang F.Inhibition of miR985p promotes high glucoseinduced suppression of preosteoblast proliferation and differentiation via the activation of the PI3K/AKT/GSK3beta signaling pathway by targeting BMP2[J].Mol Med Rep,2022,26(3):292.
[9] Guidotti S,Minguzzi M,Platano D,et al.Glycogen synthase kinase-3beta inhibition links mitochondrial dysfunction,extracellular matrix remodelling and terminal differentiation in chondrocytes[J].Sci Rep,2017,7(1):12059.
[10] Agarwal P,Lee HP,Smeriglio P,et al.A dysfunctional TRPV4-GSK3beta pathway prevents osteoarthritic chondrocytes from sensing changes in extracellular matrix viscoelasticity[J].Nat Biomed Eng,2021,5(12):1472-1484.
[11] Lee HP,Stowers R,Chaudhuri O.Volume expansion and TRPV4 activation regulate stem cell fate in three-dimensional microenvironments[J].Nat Commun,2019,10(1):529.
[12] Wisdom KM,Adebowale K,Chang J,et al.Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments[J].Nat Commun,2018,9(1):4144.
[13] Zhu Y,Ye L,Cai X,et al.Icariin-loaded hydrogel regulates bone marrow mesenchymal stem cell chondrogenic differentiation and promotes cartilage repair in osteoarthritis[J].Front Bioeng Biotechnol,2022,10:755260.
[14] Huang PY,Wu JG,Gu J,et al.Bioinformatics analysis of miRNA and mRNA expression profiles to reveal the key miRNAs and genes in osteoarthritis[J].J Orthop Surg Res,2021,16(1):63.
[15] Shang X,Boker KO,Taheri S,et al.The interaction between microRNAs and the Wnt/beta-catenin signaling pathway in osteoarthritis[J].Int J Mol Sci,2021,22(18):9887.
[16] Le LT,Swingler TE,Crowe N,et al.The microRNA-29 family in cartilage homeostasis and osteoarthritis[J].J Mol Med(Berl),2016,94(5):583-596.
[17] Liu J,Tang G,Liu W,et al.MiR-20a-5p facilitates cartilage repair in osteoarthritis via suppressing mitogen-activated protein kinase kinase kinase 2[J].Bioengineered,2022,13(5):13801-13814.
[18] Wu T,Tang H,Yang J,et al.METTL3-m(6)A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway[J].Cell Prolif,2022,55(5):e13234.
[19] 梁朝鑫,周安远,王 伟,等.骨髓间充质干细胞治疗骨科疾病研究进展[J].陕西医学杂志,2022,51(1):121-124,129.
[20] Bai H,Zhao Y,Wang C,et al.Enhanced osseointegration of three-dimensional supramolecular bioactive interface through osteoporotic microenvironment regulation[J].Theranostics,2020,10(11):4779-4794.
[21] 栾彦军,王 磊,贾 戊.桃叶珊瑚苷在体外抑制白细胞介素-1β诱导的软骨细胞凋亡及减缓小鼠骨关节炎疾病进展实验研究[J].陕西医学杂志,2022,51(9):1055-1059,1065.
[22] 徐 翀,申利民,苑文杰.当归多糖通过Wnt/β-catenin信号通路抑制骨关节炎软骨细胞氧化应激损伤与炎症反应[J].陕西中医,2022,43(6):700-703,770.

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备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区自然科学基金资助项目(2020D01C198)
更新日期/Last Update: 2023-06-05