ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis.
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.
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Bing-Yun
BY
Li
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Yan-Hui
YH
Gao
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Jun-Rui
JR
Pei
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Yan-Mei
YM
Yang
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Wei
W
Zhang
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Dian-Jun
DJ
Sun
D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D009050:Fluorosis, Dental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015870:Gene Expression; D006706:Homeostasis; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D013662:Tea / Q000737:chemistry*
D015415:Biomarkers; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; C509143:OSTM1 protein, mouse; D010936:Plant Extracts; D059808:Polyphenols; D020011:Protective Agents; D013662:Tea