Objective To investigate the role of hedgehog (Hh) signaling pathway on cartilage tissue damage in rats with chronic fluorosis.
Methods Thirty-six healthy Sprague-Dawley (SD) rats were randomly divided into three groups (6 males and 6 females in each group): a control group (supplied with drinking water containing sodium fluoride NaF of < 1 mg/L) and two fluorosis groups (supplied with drinking water containing NaF of 5 and 50 mg/L). By the end of 6 months’ treatment, fluorine content in urine and bone of the rats were detected with fluorin-ion electrode method. Histological changes in cartilage tissues were observed with light microscope using hematoxylin and eosin (HE) staining. Protein components of the Hh signaling pathway, including sonic hedgehog (Shh), smoothened (Smo) and bone morphogenetic protein-2 (BMP-2), as well as apoptosis-regulating proteins B cell lymphoma/leukemia-2 (Bcl-2) and B cell lymphoma/leukemia gene associated x protein (Bax), were detected using immunohistochemistry staining and Western blot.
Results The fluorine contents in the urine (3.66 ± 0.43 and 8.05 ± 0.60 mg/L) and bone (402.38 ± 33.77 and 935.12 ± 49.60 mg/kg) of the rats of low and high-dose fluoride groups were higher than those of the rats of control group (P < 0.05 for all). Thinned metaphysic cartilage of stifles, decreased count of chondrocytes, and signs of sclerotic skeletal fluorosis were observed in the rats with fluorine treatment. Compared with those of the control rats, significantly increased protein expression of Shh (0.86 ± 0.09 and 1.11 ± 0.15), Smo (0.92 ± 0.11 and 1.17 ± 0.14), BMP-2 (1.02 ± 0.14 and 1.13 ± 0.12), Bax (0.91 ± 0.14 and 0.92 ± 0.11) and decreased protein expression of Bcl-2 (0.78 ± 0.03 and 0.57 ± 0.09) were detected in the rats treated with low and high dose fluorine (P < 0.05 for all).
Conclusion The activation of Hh signaling pathway and excessive expression of the downstream target genes may become pathogenesis of chondrocyte damage in chronic fluorosis in rats.
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