Department of Stomatology, the Central Hospital afilliated to Shandong First Medical University, Jinan, 250013, China.
Department of Ophthalmology, the Jinan Eighth Hospital, Jinan, 250013, China.
Arch Oral Biol. 2020 May;113:104713. doi: 10.1016/j.archoralbio.2020.104713. Epub 2020 Mar 20.
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.
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.
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).
Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/β-catenin pathway.
本研究旨在探讨过表达微小 RNA-141(miR-141)对去卵巢诱导骨质疏松症大鼠颌骨的影响,并研究 miR-141 在 Wnt/β-catenin 通路中的作用。
将 24 只雌性大鼠随机分为假手术组、去卵巢骨质疏松组(OP)、miR-141 激动剂组(miR-141)和 miR-141 对照 scramble 组(Scramble)。检测颌骨骨密度(BMD)和病理变化。采用 ELISA 法检测血清核因子κB 受体激活物配体(RANKL)、护骨素、抗酒石酸酸性磷酸酶(TRAP)和骨钙素(BGP)水平。采用免疫组化法检测 Runt 相关转录因子 2(Runx2)和成骨特异性转录因子 2(Osterix)的表达,采用 Western blot 法检测 Wnt、β-catenin 和 Dickkopf1(DKK1)蛋白的表达。进一步用 Wnt 激动剂 DKK2-C2、Wnt 抑制剂恩度验证 miR-141 过表达对 Wnt/β-catenin 通路的影响。
与 OP 组相比,miR-141 和 DKK2-C2 组护骨素含量增加,RANKL、BGP、TRAP 水平降低(p<0.05)。miR-141 和 DKK2-C2 组 Runx2 和 Osterix 水平明显高于 OP 组(p<0.05)。有趣的是,与 OP 组相比,miR-141 和 DKK2-C2 组 Wnt 和 β-catenin 蛋白表达增加,DKK1 表达明显下调(p<0.05)。与 miR-141 组相比,用恩度治疗后,上述结果逆转(p<0.05)。
过表达 miR-141 可通过激活 Wnt/β-catenin 通路抑制去卵巢大鼠颌骨骨质疏松症。