Li Bing-Yun, Gao Yan-Hui, Pei Jun-Rui, Yang Yan-Mei, Zhang Wei, Sun Dian-Jun
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Int J Mol Med. 2017 May;39(5):1155-1163. doi: 10.3892/ijmm.2017.2933. Epub 2017 Mar 22.
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 transmembrane 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.
流行病学调查表明，茶砖中的某些成分可以对抗氟的不良影响。茶多酚（TPs）是茶砖中生物活性最高的成分，已被证明是有效的骨骼支持剂。已知氯离子通道蛋白7（ClC‑7）对破骨细胞（OC）的骨吸收至关重要。因此，在本研究中，我们使用小鼠模型研究了TPs对氟中毒的潜在保护作用，并特别关注ClC‑7探索其潜在机制。总共40只3周龄健康雄性C57BL/6小鼠按体重随机分为4组（每组n = 10），如下：蒸馏水（对照组）、100 mg/l氟化水（F组）、含10 g/l TPs的水（TP组）和含100 mg/l氟化物和10 g/l TPs的水（F + TP组）。15周后，处死小鼠，取出长骨，体外培养骨髓来源的巨噬细胞以进行多项实验。通过抗酒石酸酸性磷酸酶（TRAP）染色鉴定并计数破骨细胞。摄入氟导致严重氟中毒和破骨细胞功能受损（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）和骨石化相关跨膜蛋白1（Ostm1）的mRNA表达降低）。在F + TP组中，氟中毒减轻，破骨细胞功能恢复，但骨氟含量仍高。与F组相比，F + TP组中的成熟破骨细胞ClC‑7和Ostm1的mRNA水平表达更高；荧光强度实验表明，Cl-的运输和保留得到改善。总体而言，我们的研究结果表明，TPs通过调节破骨细胞的骨吸收减轻C57BL/6小鼠的氟中毒。氟通过抑制ClC‑7和Ostm1抑制破骨细胞吸收，而TPs减弱氟的这种抑制作用。
