Role of inhibition of osteogenesis function by Sema4D/Plexin-B1 signaling pathway in skeletal fluorosis in vitro.

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-B1 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-ß1 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-ß1 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.

The influence of fluoride on the expression of inhibitors of Wnt/ß-catenin signaling pathway in rat skin fibroblast Cells.

The effective therapy of fluoride-induced bone diseases requires an understanding of the mechanism of the disorders. Changes in the inhibitors of the Wnt/ß-catenin pathway, Dickkopf-1 (Dkk-1) and Sclerostin (SOST),were studied in supernatants harvested from rat skin fibroblasts cultured with varied doses of fluoride. The contents of SOST and Dkk-1 in fibroblast supernatants were assessed at four exposure time-points and investigated by using the method of ELISA. Compared to the relevant controls(0 mg F(−)/L), a significant decrease of the concentrations of SOST and Dkk-1 was observed as the fluoride concentration increased. Compared to the relevant time controls (24 h), a significant decrease of the concentrations of SOST and Dkk-1 was observed with the extension of time. Our results suggest that the Wnt/ß-catenin pathway inhibitors Dkk-1 and SOST play an important role in skeletal fluorosis. They can be used as important indications for diagnosing bone metabolism changes caused by fluoride exposure and therapeutic targets in diseases resulting from fluoride exposure.

Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP.

OBJECTIVE: To analyze the changes in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BALP) activity and changes in osteocalcin (BGP) content following fluoride exposure and, thereby, determine the reference indications of fluoride-induced changes in bone metabolism. METHODS: In the animal study, rats were allowed free access to drinking water containing different concentrations (10, 150, or 400 mg/L) of sodium fluoride. Serum ALP and BALP activity and serum BGP content were assessed at three exposure time-points. In the spot study, serum ALP and BALP activity and serum BGP content were assessed in workers exposed to fluoride in their working environment for different periods of time. RESULTS: Compared with the control group, on days 15 and 30, the activity of serum ALP in the low- and medium-dose group was significantly higher (p < 0.05), while in the high-dose group it was significantly lower (p < 0.05). Only on day 30 was the activity of serum BALP in the medium-dose group significantly higher than that of the control group (p < 0.05). BGP content was lower in the high-dose group than in the control group (p < 0.05) on days 30 and 90, but it was higher in the medium-dose group on day 90. Compared with the control group, BGP content in the fluoride-exposed group was higher (p < 0.05). In the spot study, serum ALP activity and serum BGP content in the medium working-age group were higher than that in the short working-age group (p < 0.05). However, serum ALP activity and serum BGP content were lower in the long working-age group than in the medium working-age group (p < 0.05). CONCLUSIONS: Our results suggest that serum fluoride and urinary fluoride can be used as reference indications to provide an overall reflection of the body's fluoride-load and fluoride exposure level. Serum ALP activity and serum BGP content can be used as important reference indications for diagnosing bone metabolism changes resulting from fluoride exposure.

[Method for concentration determination of mineral-oil fog in the air of workplace].

OBJECTIVE: To study the method of concentration determination of mineral-oil fog in the air of workplace. METHODS: Four filter films such as synthetic fabric filter film, beta glass fiber filter film, chronic filter paper and microporous film were used in this study. Two kinds of dust samplers were used to collect the sample, one sampling at fast flow rate in a short time and the other sampling at slow flow rate with long duration. Subsequently, the filter membrane was weighed with electronic analytical balance. According to sampling efficiency and incremental size, the adsorbent ability of four different filter membranes was compared. RESULTS: When the flow rate was between 10 approximately 20 L/min and the sampling time was between 10 approximately 15 min, the average sampling efficiency of synthetic fabric filter film was 95.61% and the increased weight ranged from 0.87 to 2.60 mg. When the flow rate was between 10 approximately 20 L/min and sampling time was between 10 approximately 15 min, the average sampling efficiency of beta glass fiber filter film was 97.57% and the increased weight was 0.75 approximately 2.47 mg. When the flow rate was between 5 approximately 10 L/min and the sampling time between 10 approximately 20 min, the average sampling efficiency of chronic filter paper and microporous film was 48.94% and 63.15%, respectively and the increased weight was 0.75 approximately 2.15 mg and 0.23 approximately 0.85 mg, respectively. When the flow rate was 3.5 L/min and the sampling time was between 100 approximately 166 min, the average sampling efficiency of filter film were 94.44% and 93.45%, respectively and the average increased weight was 1.28 mg for beta glass fiber filter film and 0.78 mg for beta glass fiber filter film and synthetic fabric synthetic fabric filter film. The average sampling efficiency of chronic filter paper and microporous film were 37.65% and 88.21%, respectively. The average increased weight was 4.30 mg and 1.23 mg, respectively. CONCLUSION: Sampling with synthetic fabric filter film and beta glass fiber filter film is credible, accurate, simple and feasible for determination of the concentration of mineral-oil fog in workplaces.