Association of Dietary Carotenoids Intake with Skeletal Fluorosis in the Coal-burning Fluorosis Area of Guizhou Province

Objective To explore whether the intake of dietary carotenoids could protect against skeletal fluorosis in Guizhou province in which coal-burning fluorosis is endemic. Methods A case-control study of 196 patients with skeletal fluorosis and 196 age and gender-matched controls was conducted in Zhijin, Guizhou Province. Face-to-face interviews were conducted to assess habitual dietary intake using a 75-item food frequency questionnaire and various covariates with structured questionnaires. Urinary fluoride was measured using an ion-selective electrode method. The genotype of superoxide dismutase 2（SOD2） rs11968525 was detected by Taq Man method. Results We observed significant dose-dependent inverse associations of skeletal fluorosis with intake of β-carotene, lutein/zeaxanthin, lycopene, and total carotenoids（P-trend = 0.002 to 0.018）, whereas α-carotene and β-cryptoxanthin intakes were not found to be related to skeletal fluorosis, after adjustment for potential confounders. The adjusted ORs and 95% CI of skeletal fluorosis for the highest versus lowest quartile were 0.30（0.10, 0.86） for β-carotene, 0.23（0.08, 0.66） for lycopene, 0.26（0.10, 0.75） for lutein/zeaxanthin and 0.34（0.14, 0.74） for total carotenoids（all P-trend ＆lt; 0.05）. Stratified analyses showed that the protective effects of lutein/zeaxanthin and total carotenoids on skeletal fluorosis were more evident for individuals with the AG＋AA genotypes of SOD2（rs11968525）. Conclusion Increased intakes of β-carotene, lutein/zeaxanthin, lycopene, and total carotenoids are independently associated with a lower risk of coal-burning skeletal fluorosis. SOD2（rs11968525） polymorphisms might modify the inverse associations between dietary carotenoids and skeletal fluorosis.

Role of Inhibition of Osteogenesis Function by Sema4D/Plexin-B1 Signaling Pathway in Skeletal Fluorosis In Vitro

Summary： Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B 1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway. Both of these processes form a feedback circuit which is a key link in skeletal fluorosis. In this study, an osteoblast-osteoclast co-culture model in vitro was developed to illustrate the mechanism of skeletal fluorosis. With the increase of fluoride concentration, the expression level of Sema4D was decreased and TGF-β1 was increased continuously. OPG/RANKL mRNA level, however, increased gradually. On the basis of that, the inhibition of Sema4D/Plexin-B1/RhoA/ROCK signaling pathway caused by fluoride promoted the level of TGF-β1 and activated the proliferation of osteoblasts. In addition, osteroprotegerin （OPG） secreted by osteoblasts was up-regulated by fluoride. The competitive combination of OPG and RANKL was strengthened and the combination of RANKL and RANK was hindered. And then the differentiation and maturation of osteoclasts were inhibited, and bone absorption was weakened, leading to skeletal fluorosis.