- Osteocytes can tolerate the toxic dose of fluoride, and PTH [Parathyroid hormone] administration significantly reduced osteocytes viability.
- PTH aggravated effect of fluoride on osteoclastogenesis related molecules in osteocytes.
- PTH administration hardly amplified the stimulating effect of fluoride on osteoclastogenesis.
- The impact of fluoride on osteocyte-driven osteoclast differentiation was stronger than that of PTH.
- The RANK-JNK-NFAtc1 signaling pathway was involved in fluoride affected osteocyte-driven osteoclastogenesis.
Excessive systemic uptake of inorganic fluorides causes disturbances of bone homeostasis. The mechanism of skeletal fluorosis is still uncertain. This study aimed to study the effect of fluoride on osteocyte-driven osteoclastogenesis and probe into the role of PTH in this process. IDG-SW3 cells seeded in collagen–coated constructs were developed into osteocyte-like cells through induction of mineral agents. Then, osteocyte-like cells were exposed to fluoride in the presence or absence of parathyroid hormone (PTH). Cell viability and their capacity to produce receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and sclerostin (SOST) were detected by MTT and Western blot assays, respectively. Finally, a transwell coculture system using osteocyte-like cells seeded in the low compartment, and osteoclast precursors added in the inserts was developed to observe the osteocyte-driven osteoclasogenesis response to fluoride with or without PTH, and the expression of molecules involved in this mechanism were measure by real time RT-PCR. Results showed that osteocytes withstood a toxic dose of fluoride, and yet PTH administration significantly reduced osteocytes viability. PTH amplified the effect of fluoride on the expression of osteoclastogenesis-related molecules in osteocyte, but did not enlarged the stimulating effect of fluoride on osteoclastogenesis drove by osteocyte coculture. Gene expression levels of TRAP, RANK, JNK and NFAtc1 significantly increased in fluoride affected osteoclast precursor cocultured with osteocyte-like cells. The impact of fluoride on osteocyte-driven osteoclast differentiation was stronger than that of PTH. In conclusion, osteocyte played a pivotal role on the mechanism underlying fluoride-affected osteoclastogenesis in which RANK-JNK-NFATc1 signaling pathway was involved, and PTH had a significant impact in this process.
*Original abstract online at https://www.sciencedirect.com/science/article/pii/S0300483X20300688?via%3Dihub
PTH (1–34) affects bone turnover governed by osteocytes exposed to fluoride
Highlights • Osteocytes endured high dose of fluoride exposure.• Fluoride inhibited expression of SOST/Sclerostin in osteocytes.• Fluoride modulated ratio of RANKL/OPG in osteocytes.• Fluoride regulated Wnt/?-catenin signaling in osteocytes.• PTH(1–34) participated in fluoride-modulating SOST and RANKL expression in osteocytes. Exposure to fluoride from environmental sources remains an overlooked, but serious public health
Is the severity of osteosclerosis of fluorosis proportional to the dose of fluoride intake?
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Histopathological assessment of endemic skeletal fluorosis
Nine patients with skeletal fluorosis were subjected to iliac crest biopsy because they presented with stiffness and bone pains. The histopathological findings are correlated with the clinical course, X-ray and laboratory data. All but one of the patients showed an increase in bone surfaces lined by osteoid and in these
Fluoride-mediated apoptosis and disordering of cell cycle distributions during in vitro organ culture of mouse fetal long bones.
Effects of fluoride (as NaF) on cell cycle, DNA content, and apoptosis of mouse fetal long bone cultures were examined and analyzed by flow cytometry (FCM). The results showed that NaF at 2.5–5.0 µg/mL (2.5–5.0 ppm) had only slight effects on the DNA content and cell cycle distributions. At 10.0
The role of TGFß receptor 1-smad3 signaling in regulating the osteoclastic mode affected by fluoride.
Highlights Fluoride upregulated 303 miRNAs expression and downregulated 61 miRNAs. Fluoride exhibited biphasic effect on osteoclast viability, formation and function. Fluoride indicated little effect on expression of RANK protein. SB431542 inhibited or aggravated fluoride-regulating osteoclast mode. Stimulation of fluoride on Smad3 expression exhibited dose-dependent manner. Studies that have focused on
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