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维生素D驱动的信号传导增加以及猫牙齿吸收中维生素D受体、MSX2和RANKL的表达增加。

Increased vitamin D-driven signalling and expression of the vitamin D receptor, MSX2, and RANKL in tooth resorption in cats.

作者信息

Booij-Vrieling Henriëtte E, Ferbus Didier, Tryfonidou Marianna A, Riemers Frank M, Penning Louis C, Berdal Ariane, Everts Vincent, Hazewinkel Herman A W

机构信息

Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

出版信息

Eur J Oral Sci. 2010 Feb;118(1):39-46. doi: 10.1111/j.1600-0722.2009.00707.x.

DOI:10.1111/j.1600-0722.2009.00707.x
PMID:20156263
Abstract

Tooth resorption occurs in 20-75% of cats (Felis catus). The aetiology is not known, but vitamin D is suggested to be involved. Vitamin D acts through a nuclear receptor (VDR) and increases the expression of receptor activator of nuclear factor-kappaB ligand (rankl) and muscle segment homeobox 2 (msx2) genes. Mice lacking the muscle segment homeobox 2 (msx2) gene show decreased levels of rankl, suggesting an interaction among VDR, MSX2, and RANKL. Here, we investigated the expression of VDR, MSX2, and RANKL proteins, and the activity of the VDR-mediated signalling pathway (using the quantitative polymerase chain reaction on VDR target genes), in tooth resorption, and measured the serum levels of vitamin D metabolites in cats. Tooth resorption was categorized into either resorptive or reparative stages. In the resorptive stage, odontoclasts expressed MSX2 and RANKL (100% and 88%, respectively) and fibroblasts expressed VDR and MSX2 (both at 100%), whereas fibroblasts expressed RANKL in only 29% of the sites analysed. In the reparative stage, cementoblasts expressed VDR, MSX2, and RANKL, whereas fibroblasts expressed VDR and MSX2, but not RANKL. The vitamin D status did not differ between the groups, based on the serum levels of 25-hydroxycholecalciferol. However, increased expression of VDR protein, and the relative gene expression levels of 1alpha-hydroxylase and the VDR-target gene, 24-hydroxylase, indicated the involvement of an active vitamin D signalling in the pathophysiology of tooth resorption in cats.

摘要

20% - 75%的猫(家猫)会发生牙齿吸收。其病因尚不清楚,但有研究表明维生素D与之有关。维生素D通过核受体(VDR)发挥作用,可增加核因子κB受体激活剂配体(RANKL)和肌肉节段同源盒2(MSX2)基因的表达。缺乏肌肉节段同源盒2(MSX2)基因的小鼠RANKL水平降低,提示VDR、MSX2和RANKL之间存在相互作用。在此,我们研究了牙齿吸收过程中VDR、MSX2和RANKL蛋白的表达,以及VDR介导的信号通路活性(通过对VDR靶基因进行定量聚合酶链反应),并测量了猫血清中维生素D代谢产物的水平。牙齿吸收分为吸收期或修复期。在吸收期,破牙细胞表达MSX2和RANKL(分别为100%和88%),成纤维细胞表达VDR和MSX2(均为100%),而成纤维细胞仅在29%的分析位点表达RANKL。在修复期,成牙骨质细胞表达VDR, MSX2和RANKL,而成纤维细胞表达VDR和MSX2,但不表达RANKL。根据25 - 羟胆钙化醇的血清水平,两组之间的维生素D状态没有差异。然而,VDR蛋白表达增加,以及1α - 羟化酶和VDR靶基因24 - 羟化酶的相对基因表达水平增加,表明活性维生素D信号参与了猫牙齿吸收的病理生理过程。

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