Effects of parathyroid hormone (1-34) on the regulation of the lysyl oxidase family in ovariectomized mice.
Effects of parathyroid hormone (1-34) on the regulation of the lysyl oxidase family in ovariectomized mice.
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甲状旁腺激素(1-34)对去卵巢小鼠赖氨酰氧化酶家族调节的影响
DOI：
10.1039/c8ra04574g
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发表时间：
2018-08-24
期刊：
影响因子：
3.9
通讯作者：
Zhou, Xuedong
中科院分区：
文献类型：
--
作者：
Cai, Linyi;Zhang, Demao;Liu, Wenjing;Cui, Yujia;Jing, Junjun;Xie, Jing;Zhou, Xuedong
骨质疏松症（Osteoporosis，OP）是一种高度流行的慢性疾病。合成代谢剂甲状旁腺激素（PTH）通常用于治疗OP，以增强骨质并降低骨折风险，尽管具体机制尚不清楚。赖氨酰氧化酶（LOX）通过催化胶原蛋白和弹性蛋白的交联而稳定有机基质。本研究通过切除C57 BL/6 J小鼠卵巢并给予PTH治疗，建立了卵巢癌模型。我们进一步的目的是确定LOX家族的表达变化，PTH的影响，在卵巢切除小鼠。我们观察到去卵巢小鼠骨量减少，骨显微结构恶化。通过μCT和HE染色证实，PTH减轻了骨组织的微结构损伤，加速了骨重建。血清铜和锌水平间接证实了这一结果。与假手术对照小鼠相比，LOX家族的五个成员的表达水平在卵巢切除小鼠中均下降（p < 0.05），并且每天注射PTH成功地逆转了OP中LOX的低表达。本研究首次检测了LOX在帕金森病小鼠和PTH治疗的帕金森病小鼠中的表达变化，LOXs的异常表达与OP的发生、发展密切相关，LOXs可能作为PTH的下游效应物，导致骨代谢失衡和骨微结构损伤。因此，LOX可能作为OP的有希望的治疗靶点。
Osteoporosis (OP) is a highly prevalent chronic disease. The anabolic agent parathyroid hormone (PTH) is often prescribed for the treatment of OP to strengthen bone quality and decrease the risk of fracture, although the specific mechanisms are still unclear. Lysyl oxidase (LOX) can stabilize the organic matrix through catalyzing the cross-linking of collagen and elastin. In this study, we established osteoporotic models via ovariectomizing C57BL/6J mice and treating them with PTH. We further aimed to determine the expression changes of the LOX family, impacted by PTH, in ovariectomized mice. We observed that bone mass was reduced and bone microstructure was deteriorative in ovariectomized mice. And PTH attenuated the microstructural damage and accelerated bone remodeling, as confirmed via μCT and HE staining. Serum levels of copper and zinc indirectly proved the results. The expression levels of five members of the LOX family all declined in ovariectomized mice compared to in sham-operated control mice (p < 0.05), and the daily injection of PTH successfully reversed the low expression of LOXs in OP. The current study examined expression changes of LOXs in osteoporotic mice and PTH-treated osteoporotic mice for the first time, and provided an important piece of evidence that the aberrant expression of LOXs had intimate associations with the occurrence and development of OP. And LOXs may act as the downstream effectors of PTH, contributing to unbalanced bone metabolism and damaged bone microstructure. Consequently, LOXs may act as promising therapeutic targets for OP.
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影响因子：
4.1
作者：
Jilka, Robert L.;O'Brien, Charles A.;Ali, A. Afshan;Roberson, Paula K.;Weinstein, Robert S.;Manolagas, Stavros C.
通讯作者：
Manolagas, Stavros C.
影响因子：
4.8
作者：
Eliades, Alexia;Papadantonakis, Nikolaos;Ravid, Katya
通讯作者：
Ravid, Katya
影响因子：
7.5
作者：
Chung JY;Song M;Ha CW;Kim JA;Lee CH;Park YB
通讯作者：
Park YB
DOI：
10.11124/jbisrir-2015-1948
发表时间：
2015-09-16
期刊：
JBI database of systematic reviews and implementation reports
影响因子：
--
作者：
Hoga, Luiza;Rodolpho, Juliana;Quirino, Bruna
通讯作者：
Quirino, Bruna
影响因子：
4.2
作者：
Alsofi L;Daley E;Hornstra I;Morgan EF;Mason ZD;Acevedo JF;Word RA;Gerstenfeld LC;Trackman PC
通讯作者：
Trackman PC