A novel function for lysyl oxidase in pluripotent mesenchymal cell proliferation and relevance to inflammation-associated osteopenia.
A novel function for lysyl oxidase in pluripotent mesenchymal cell proliferation and relevance to inflammation-associated osteopenia.
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DOI：
10.1371/journal.pone.0100669
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Trackman PC
中科院分区：
文献类型：
--
作者：
Khosravi R;Sodek KL;Xu WP;Bais MV;Saxena D;Faibish M;Trackman PC
赖氨酰氧化酶是胶原蛋白生物合成所必需的多功能酶。多种生长因子在成骨细胞分化过程中调节赖氨酰氧化酶，在包括糖尿病骨疾病在内的炎症性骨质疏松性疾病中受细胞因子如肿瘤坏死因子-α的调节。规范的Wnt信号促进成骨细胞的发育。在这里，我们研究了WNT3a和肿瘤坏死因子-α对多能C3H10T1/2细胞、骨髓基质细胞和定向成骨细胞赖氨酰氧化酶表达的影响。赖氨酰氧化酶在C3H10T1/2细胞中通过转录机制上调3倍，在骨髓基质细胞中上调2.5倍。在赖氨酰氧化酶启动子中发现了一个可能具有功能的Tcf/Lef元件。有趣的是，赖氨酰氧化酶在承诺的原代大鼠颅骨或MC3T3-E1成骨细胞中并没有上调。肿瘤坏死因子-α通过miR203介导的转录后机制下调WNT3a处理和未处理的C3H10T1/2细胞中赖氨酸氧化酶的表达。未分化的细胞不产生胶原基质；因此，研究了赖氨酰氧化酶在多能细胞中的新的生物学作用。赖氨酰氧化酶shRNAs能有效抑制赖氨酰氧化酶的表达，抑制C3H10T1/2细胞生长达50%，并阻断成骨细胞的分化。我们认为，在糖尿病、骨质疏松症或类风湿性关节炎等过度炎症条件下干扰赖氨酰氧化酶的表达可能会导致多能细胞池减少，最终导致骨量减少。
Lysyl oxidase is a multifunctional enzyme required for collagen biosynthesis. Various growth factors regulate lysyl oxidase during osteoblast differentiation, subject to modulation by cytokines such as TNF-α in inflammatory osteopenic disorders including diabetic bone disease. Canonical Wnt signaling promotes osteoblast development. Here we investigated the effect of Wnt3a and TNF-α on lysyl oxidase expression in pluripotent C3H10T1/2 cells, bone marrow stromal cells, and committed osteoblasts. Lysyl oxidase was up-regulated by a transcriptional mechanism 3-fold in C3H10T1/2 cells, and 2.5-fold in bone marrow stromal cells. A putative functional TCF/LEF element was identified in the lysyl oxidase promoter. Interestingly, lysyl oxidase was not up-regulated in committed primary rat calvarial- or MC3T3-E1 osteoblasts. TNF-α down-regulated lysyl oxidase both in Wnt3a-treated and in non-treated C3H10T1/2 cells by a post-transcriptional mechanism mediated by miR203. Non-differentiated cells do not produce a collagen matrix; thus, a novel biological role for lysyl oxidase in pluripotent cells was investigated. Lysyl oxidase shRNAs effectively silenced lysyl oxidase expression, and suppressed the growth of C3H10T1/2 cells by 50%, and blocked osteoblast differentiation. We propose that interference with lysyl oxidase expression under excess inflammatory conditions such as those that occur in diabetes, osteoporosis, or rheumatoid arthritis can result in a diminished pool of pluripotent cells which ultimately contributes to osteopenia.
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DOI：
10.1038/nrm3528
发表时间：
2013-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.8
作者：
Atsawasuwan, Phimon;Mochida, Yoshiyuki;Yamauchi, Mitsuo
通讯作者：
Yamauchi, Mitsuo
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
影响因子：
6.1
作者：
Choi, Sun-Sil;Cha, Byung-Yoon;Woo, Je-Tae
通讯作者：
Woo, Je-Tae
影响因子：
4.1
作者：
Jackson, A;Vayssière, B;Rawadi, G
通讯作者：
Rawadi, G