ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis.
ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis.
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DOI：
10.3892/ijmm.2017.2933
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发表时间：
2017-05
影响因子：
5.4
通讯作者：
Sun DJ
中科院分区：
文献类型：
--
作者：
Li BY;Gao YH;Pei JR;Yang YM;Zhang W;Sun DJ
流行病学调查表明，茶砖中的某些成分可以对抗氟化物的不良影响。茶多酚（TPs）是茶砖中最具生物活性的成分，已被证明是有效的骨支持剂。已知ClC-7对破骨细胞（OC）骨吸收至关重要。因此，在本研究中，我们通过小鼠模型研究了TPs对氟中毒的潜在保护作用，并探讨了其潜在机制，特别是对ClC-7的关注。选取健康3周龄雄性C57BL/6小鼠40只，按体重随机分为蒸馏水组（对照组）、100 mg/l氟化水组（F组）、10 g/l TPs水组（TP组）和100 mg/l氟+ 10 g/l TPs水组（F + TP组），每组10只。15周后，处死小鼠，取出长骨，体外培养骨髓源性巨噬细胞，进行多次实验。通过抗酒石酸酸性磷酸酶（TRAP）染色对OCs进行鉴定和计数。氟的摄入导致严重氟中毒和OC功能受损[骨吸收受损，活化t细胞核因子1 （NFATc1）、atp酶H+转运V0亚基D2 （ATP6v0d2）和骨质疏松相关跨膜蛋白1 (Ostm1) mRNA表达降低]。在F + TP组，氟中毒减轻，OC功能恢复，但没有高骨氟化物含量。与F组比较，F + TP组成熟OCs中ClC-7和Ostm1 mRNA表达水平升高；荧光强度实验表明，氯离子的运输和保留得到了改善。总的来说，我们的研究结果表明，TPs通过调节OC骨吸收来减轻C57BL/6小鼠氟中毒。氟通过抑制ClC-7和Ostm1来抑制OC的吸收，而TPs则减弱了氟的这种抑制作用。
Epidemiological investigations indicate that certain ingredients in tea bricks can antagonize the adverse effects of fluoride. Tea polyphenols (TPs), the most bioactive ingredient in tea bricks, have been demonstrated to be potent bone-supporting agents. ClC-7 is known to be crucial for osteoclast (OC) bone resorption. Thus, in this study, we investigated the potential protective effects of TPs against fluorosis using a mouse model and explored the underlying mechanisms with particular focus on ClC-7. A total of 40, healthy, 3-week-old male C57BL/6 mice were randomly divided into 4 groups (n=10/group) by weight as follows: distilled water (control group), 100 mg/l fluoridated water (F group), water containing 10 g/l TPs (TP group) and water containing 100 mg/l fluoride and 10 g/l TPs (F + TP group). After 15 weeks, and after the mice were sacrificed, the long bones were removed and bone marrow-derived macrophages were cultured ex vivo in order to perform several experiments. OCs were identified and counted by tartrate-resistant acid phosphatase (TRAP) staining. The consumption of fluoride resulted in severe fluorosis and in an impaired OC function [impaired bone resorption, and a low mRNA expression of nuclear factor of activated T-cells 1 (NFATc1), ATPase H+ transporting V0 subunit D2 (ATP6v0d2) and osteopetrosis-associated trans-membrane protein 1 (Ostm1)]. In the F + TP group, fluorosis was attenuated and OC function was restored, but not the high bone fluoride content. Compared with the F group, mature OCs in the F + TP group expressed higher mRNA levels of ClC-7 and Ostm1; the transportation and retaining of Cl− was improved, as shown by the fluorescence intensity experiment. On the whole, our findings indicate that TPs mitigate fluorosis in C57BL/6 mice by regulating OC bone resorption. Fluoride inhibits OC resorption by inhibiting ClC-7 and Ostm1, whereas TPs attenuate this inhibitory effect of fluoride.