ArticleJournal of orthopaedic surgery and research2021
The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury.
Article in Journal of orthopaedic surgery and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Rosa roxburghii Tratt Juice Inhibits Fluoride Exposure-Induced Bone Damage in Male Rats by Regulating the Homeostasis of the ROS/TNF-α/NF-κB Pathway.Biological trace element research · 2026Article
- Knockdown of SMYD3 by RNA Interference Regulates the Expression of Autophagy-Related Proteins and Inhibits Bone Formation in Fluoride-Exposed Osteoblasts.Biological trace element research · 2025Article
- Fluoride induces osteoblast autophagy by inhibiting the PI3K/AKT/mTOR signaling pathwayExperimental biology and medicine (Maywood, N.J.) · 2023Article
- Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours-A Research Hypothesis.International journal of molecular sciences · 2023Review
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
objectiveThis study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury.
methodsHealthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation.
resultsThe proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months' intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant.
conclusionHh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.
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