Fluoride Exposure Modulates Skeletal Development and Mineralization in Zebrafish Larvae

IF 4.4 3区医学 Q2 ENVIRONMENTAL SCIENCES

Environmental Toxicology Pub Date : 2025-01-25 DOI:10.1002/tox.24474

Harsheema Ottappilakkil, Ekambaram Perumal

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引用次数: 0

Abstract

The presence of high levels of fluoride (F) in groundwater is a major issue worldwide. Although F is essential for healthy teeth and bones, excessive exposure can cause fluorosis or F toxicity. This condition primarily affects the hard tissues due to their high F retention capacity. F accumulation alters bone formation and resorption mechanisms interfering with mineral homeostasis and eventually manifests as skeletal fluorosis. Albeit the numerous studies on skeletal fluorosis, the effect of F on developmental osteogenesis is inconclusive. In light of this, we studied the effect of F on osteogenic differentiation, bone development, and mineralization in zebrafish. Zebrafish embryos were subjected to a low (25 ppm NaF), and a moderately high (50 ppm NaF) dose, along with a control (E3 medium alone) until 7 days postfertilization (dpf). The F content in the larvae was quantified to reveal a dose‐dependent increase in the exposed groups. Alizarin Red and alkaline phosphatase (ALP) staining suggested enhanced mineralization in the F‐treated groups. Quantitative analyses of the ALP activity and hydroxyproline (Hyp) content revealed similar results. Alcian blue staining of pharyngeal cartilages showed that F exposure alters the morphology of the major cartilages, indicating a possible craniofacial defect. Moreover, gene expression analyses of the bone markers associated with osteogenic differentiation, early mineralization, and remodeling (runx2a/b, bmp4, ocn, osx, col1a1, alp, rank, rankl, and opg) showed enhanced expression in the low F group. While the 50 ppm F group showed a decline in osteogenic activity, a considerable increase in the expression of mineralization markers was observed. The expression levels of cartilage markers sox9a and sox9b, remained insignificant, indicating the effect of F toxicity on osteogenesis and mineralization. Also, F exposure interferes with bone metabolism through altered osteogenic differentiation, development, and mineralization in zebrafish larvae.

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来源期刊

Environmental Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

8.90%

发文量

261

审稿时长

4.5 months

期刊介绍： The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.