DEC1 deficiency results in accelerated osteopenia through enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.
DEC1 deficiency results in accelerated osteopenia through enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.
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DEC1 缺乏通过增强 DKK1 活性和减弱 PI3KCA/Akt/GSK3β 信号传导导致加速骨质减少。
DOI：
10.1016/j.metabol.2021.154730
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
He S;Guan Y;Wu Y;Zhu L;Yan B;Honda H;Yang J;Liu W
人类分化胚胎软骨细胞表达基因1 （DEC1）与促进骨形成有关，这是对抗骨发育迟缓、骨质减少和骨质疏松等骨形成失调的理想结果。DEC1敲除（KO）和年龄匹配的野生型（WT）小鼠进行了DEC1缺乏对骨发育和骨质减少的影响作为年龄的函数。在4周龄和24周龄小鼠中，DEC1缺乏表现为骨发育迟缓和骨质减少表型。然而，骨质减少在24周龄组更为严重。从机制上讲，DEC1缺乏下调Runx2和β-catenin等骨增强基因的表达，同时上调DKK1 （Wnt/β-catenin信号通路的抑制剂）。与此一致的是，DEC1缺失有利于PI3KCA/Akt/GSK3β信号通路的衰减，这是一个靶向β-catenin降解的途径。同样，24周龄组的衰减更大。然而，这些变化在体内用氯化锂（一种β-catenin的稳定剂）处理后被逆转，并通过DEC1转染DEC1 KO骨髓间充质干细胞的功能获得研究和siDEC1慢病毒感染相应WT细胞的功能丧失研究得到证实。DEC1是一种正向调节因子，在骨骼发育和维持中具有广泛的活性谱，DEC1缺乏加速的骨质减少表型通过增强DKK1活性和减弱PI3KCA/Akt/GSK3β信号来实现。
Human differentiated embryonic chondrocyte expressed gene 1 (DEC1) has been implicated in enhancing osteogenesis, a desirable outcome to counteract against deregulated bone formation such as retarded bone development, osteopenia and osteoporosis. DEC1 knockout (KO) and the age-matched wild-type (WT) mice were tested for the impact of DEC1 deficiency on bone development and osteopenia as a function of age. DEC1 deficiency exhibited retarded bone development at the age of 4 weeks and osteopenic phenotype in both 4- and 24-week old mice. However, the osteopenia was more severe in the 24-week age groups. Mechanistically, DEC1 deficiency downregulated the expression of bone-enhancing genes such as Runx2 and β-catenin accompanied by upregulating DKK1, an inhibitor of the Wnt/β-catenin signaling pathway. Consistently, DEC1 deficiency favored the attenuation of the integrated PI3KCA/Akt/GSK3β signaling, a pathway targeting β-catenin for degradation. Likewise, the attenuation was greater in the 24-week age group. These changes, however, were reversed by in vivo treatment with lithium chloride, a stabilizer of β-catenin, and confirmed by gain-of-function study with DEC1 transfection into DEC1 KO bone marrow mesenchymal stem cells and loss-of-function study with siDEC1 lentiviral infection into the corresponding WT cells. DEC1 is a positive regulator with a broad activity spectrum in both bone development and maintenance, and the osteopenic phenotype accelerated by DEC1 deficiency is achieved by enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.
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淫羊藿苷可防止糖皮质激素诱导的骨质疏松症，增加骨增强剂 DEC1 的表达并调节 PI3K/Akt/GSK3β/β-连环蛋白整合信号通路。
影响因子：
5.8
作者：
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影响因子：
6.2
作者：
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影响因子：
4.8
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作者：
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4.6
作者：
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通讯作者：
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