Down Regulation of Differentiated Embryo-Chondrocyte Expressed Gene 1 is Related to the Decrease of Osteogenic Capacity

Down Regulation of Differentiated Embryo-Chondrocyte Expressed Gene 1 is Related to the Decrease of Osteogenic Capacity
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分化胚胎软骨细胞表达基因1的下调与成骨能力下降有关

DOI:
10.2174/1389450114666140102133719
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发表时间:
2014-04-01
影响因子:
3.2
通讯作者:
Yang Jian
Yang Jian
中科院分区:
医学4区
文献类型:
--
作者:
Hu Jinhua;Mao Zhao;Yang Jian

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分化胚胎-软骨细胞表达基因1(DEC1)与软骨发生、神经发生、免疫反应、生物节律、脂肪生成、细胞分化和肿瘤发生有关。然而,关于其在成骨细胞成骨中的作用的信息很少。在本研究中,我们报道了DEC1的表达随着矿化程度的增加而增加,这与SAOS-2细胞成骨诱导时间的增加是平行的。地塞米松(DEX)可降低碱性磷酸酶(ALP)活性和矿化等成骨能力,同时降低DEC1的表达。相反,17β-雌二醇(E_2)在增加DEC1表达的同时促进成骨。此外,DEC1的过表达使ALP活性和矿化同步增加,不仅部分逆转了DEX诱导的ALP活性下降,而且几乎完全消除了DEX诱导的矿化结节减少。另一方面,与假手术组相比,去卵巢小鼠胫骨骨髓侧DEC1的表达减少,而E2治疗改善了双侧卵巢切除所致的DEC1表达的降低,从而预防了去卵巢小鼠的骨质疏松。综上所述,DEC1表达下调与成骨能力下降有关。这一发现为骨质疏松症的治疗提供了新的靶点。
Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is associated with chondrogenesis, neurogenesis, immune response, biological rhythm, lipogenesis, cell differentiation and carcinogenesis. However, there is little information about its contribution to osteoblast osteogenesis. In the present study, we report that DEC1 expression increases along with the degree of mineralization, which parallells with the increase of osteogenesis induction time in SaoS-2 cells. Dexamethasone (DEX) decreases the osteogenesis capacity such as alkaline phosphatase (ALP) activity and mineralization along with decreasing the DEC1 expression. On the contrary, 17 beta-estradiol (E2) increases the osteogenesis along with increasing the DEC1 expression. Moreover, the overexpression of DEC1 alone increases the ALP activity and mineralization synchronously, and it not only partially reverses the decrease of ALP activity induced by DEX, but almost abolishes the decrease of mineralized nodules induced by DEX. On the other hand, the DEC1 expression decreases in tibia bone marrow side of ovariectomy mice compared with that in sham-operated mice, and E2 treatment ameliorates the decrease of DEC1 expression induced by bilateral ovariectomy and prevents osteoporosis in ovariectomized mice. Taken together, downregulation of DEC1 expression is related to the decrease of osteogenic capacity. The findings provide a novel target for the therapy of osteoporosis.