ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis

Abstract

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.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

“…Functionally, both ABCC1 and BEST1 are responsible for transporting ion, and lower expression of them may increase the accumulation of fluorine in VSMCs. The results are in a way consistent with our previous study that chloride channel 7 in fluoride treated osteoclasts was significantly lower than the control group [18]. Taken together, the above results provide more evidences regarding the response of VSMCs to fluoride.…”

Fluoride impairs vascular smooth muscle cells via disrupting amino acids metabolism

“…Functionally, both ABCC1 and BEST1 are responsible for transporting ion, and lower expression of them may increase the accumulation of fluorine in VSMCs. The results are in a way consistent with our previous study that chloride channel 7 in fluoride treated osteoclasts was significantly lower than the control group(Li et al, 2017). Taken together, the above results provide more evidences regarding the response of VSMCs to fluoride.While endothelial cells (ECs) are commonly recognized as the primary guardians against vascular diseases, it's essential to appreciate the central role that VSMCs play within the cardiovascular system.…”

Multifunctional Scaffold for Osteoporotic Pathophysiological Microenvironment Improvement and Vascularized Bone Defect Regeneration

“…However, when the RANKL and M-CSF exceed the normal range, osteoclast differentiation is excessively activated and causes the hyperfunction of bone resorption. [36,37] When the MAPK kinases, such as ERK, JNK, and P38, are phosphorylated, they would enter the nucleus to accelerate osteoclast differentiation. [38,39] NF-𝜅B is mediated by P65 and exerts as a pivotal transcription factor after entry into the nucleus, which is closely associated with osteoclast differentiation.…”