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Overexpression of microRNA-141 inhibits osteoporosis in the jawbones of ovariectomized rats by regulating the Wnt/β-catenin pathway.

microRNA-141过表达通过调控Wnt/β-catenin通路抑制去卵巢大鼠颌骨骨质疏松

  • 影响因子:1.98
  • DOI:10.1016/j.archoralbio.2020.104713
  • 作者列表:"Liu TJ","Guo JL
  • 发表时间:2020-05-01
Abstract

OBJECTIVE:This work was aimed to investigate the effect of microRNA-141 (miR-141) overexpression in the jawbones of ovariectomized-induced osteoporosis rats and investigate the role of miR-141 in the Wnt/β-catenin pathway. METHODS:Twenty-four female rats were randomly divided into the sham group, ovariectomized osteoporosis group (OP), miR-141 agonist group (miR-141), and miR-141 scramble group (Scramble). Bone mineral density (BMD) and pathological changes of the jaw were detected. Serum receptor activator of nuclear factor-B ligand (RANKL), osteoprotegerin, tartrate-resistant acid phosphatase (TRAP), and bone gla protein (BGP) levels were tested by ELISA. The expression of Runt-related transcription factor 2 (Runx2), and Osterix measured by immunohistochemistry and the expression of Wnt, β-catenin, and Dickkopf1 (DKK1) proteins was measured by Western blot. Furhter, the Wnt agonist DKK2-C2, Wnt inhibitor Endostar were used to verify the effect of miR-141 overexpression on the Wnt/β-catenin pathway. RESULT:Compared with the OP group, the content of osteoprotegerin increased while the levels of RANKL, BGP, TRAP decreased in the miR-141 and DKK2-C2 groups (p < 0.05). The levels of Runx2 and Osterix increased significantly in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). Interestingly, the protein expression of Wnt and β-catenin increased while DKK1 was remarkably down-regulated in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). In contrast to the miR-141 group, the above results were reversed after treatment with the Endostar (p < 0.05). CONCLUSION:Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/β-catenin pathway.

摘要

目的: 研究microRNA-141 (miR-141) 在去势骨质疏松大鼠颌骨中的过表达,探讨miR-141在Wnt/β-catenin通路中的作用。 方法: 24只雌性大鼠随机分为假手术组、去卵巢骨质疏松组 (OP组) 、miR-141激动剂组 (miR-141) 和miR-141加乱组 (scramble组)。检测颌骨的骨密度 (BMD) 和病理学改变。采用ELISA法检测血清核因子B受体活化因子配体 (RANKL) 、骨保护素、抗酒石酸酸性磷酸酶 (TRAP) 和骨钙素 (BGP) 水平。免疫组化法测定Runt相关转录因子2 (Runx2) 和Osterix的表达,Western blot法测定Wnt、 β-catenin和Dickkopf1 (DKK1) 蛋白的表达。Furhter,Wnt激动剂DKK2-C2,Wnt抑制剂Endostar用于验证miR-141过表达对Wnt/β-catenin通路的影响。 结果: 与OP组比较,miR-141组和DKK2-C2组骨保护素含量升高,RANKL、BGP、TRAP水平降低 (p <0.05)。与OP组相比,miR-141和DKK2-C2组的Runx2和Osterix水平显著增加 (p <0.05)。有趣的是,与OP组相比,miR-141和DKK2-C2组Wnt和 β-catenin的蛋白表达增加,而DKK1显著下调 (p <0.05)。与miR-141组相比,恩度治疗后上述结果逆转 (p <0.05)。 结论: miR-141过表达可通过激活Wnt/β-catenin通路抑制去卵巢大鼠颌骨骨质疏松。

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DOI:10.1016/j.ajog.2019.08.024
作者列表:["Sutkin G","Zyczynski HM","Sridhar A","Jelovsek JE","Rardin CR","Mazloomdoost D","Rahn DD","Nguyen JN","Andy UU","Meyer I","Gantz MG","NICHD Pelvic Floor Disorders Network."]

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DOI:10.1016/j.ajog.2019.08.035
作者列表:["Zuckerwise LC","Craig AM","Newton JM","Zhao S","Bennett KA","Crispens MA"]

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发表时间:2020-01-01
DOI:10.1111/1471-0528.15932
作者列表:["Rabasa J","Bradbury M","Sanchez-Iglesias JL","Guerrero D","Forcada C","Alcalde A","Pérez-Benavente A","Cabrera S","Ramon-Cajal S","Hernandez J","Dinares C","García A","Centeno C","Gil-Moreno A"]

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