The effects of chronic glyphosate exposure on osteoblast cell function

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Justin McGehee (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Karen Katula

Abstract: Glyphosate is the functional component of the herbicide, RoundUp®. Although considered safe for humans by the US Environmental Protection Agency (EPA), it has been classified as “probably carcinogenic to man” by the International Agency for Research on Cancer (IARC). As such, the cellular effects of glyphosate require further study. This study was carried out to examine the role that glyphosate plays in altering human osteoblast cell function. We examined the effects of glyphosate (0.0007, 0.007, and 0.07 mg/ml) on human osteoblast cells (hFOB 1.19) for changes in proliferation rate, level of oxidative stress (ROS), glutathione (GSH) generation, and the expression of genes related to osteoblast differentiation and DNA methylation. This study was carried out to examine the role that glyphosate plays in altering human osteoblast cell function. Chronic glyphosate exposure caused a significant increase in proliferation in hFOB 1.19 in a dose dependent manner. The lower concentrations of exposure had the greatest effect on proliferative rate, with 0.007 mg/ml having the most pronounced effect. Levels of cellular ROS and GSH remained unchanged following chronic exposure. Expression of the transcription factors Osterix and RUNX2, markers for osteoblast differentiation, showed no significant change relative to the control. Similarly, no significant change was observed in Osteocalcin, a bone-specific protein synthesized by osteoblasts and early marker of in vitro osteogenic differentiation. However, a trending increase was observed at the lowest glyphosate concentration of 0.0007 mg/ml. While no significant changes were observed in these markers for differentiation, a significant increase in osteoblast mineralization was observed at 0.0007 and 0.007 mg/ml. Further, by Day 7 of treatment, alkaline phosphatase activity was significantly increased across all treatment groups, indicating that glyphosate enhances osteoblast differentiation. The expression of each DNA methyltransferase (DNMT1/3a/3b), proteins that catalyze the addition of methyl groups to DNA, remained unchanged across all treatment groups. Finally, a significant increase was observed in global DNA methylation at 0.0007 mg/ml, suggesting that glyphosate is an effector of DNA methylation. While our current research is ongoing, the present findings indicate that glyphosate significantly alters osteoblast proliferation and differentiation in a dose dependent manner, however more research must be conducted to elucidate the molecular basis for these changes. This study contributes to the ongoing research into the potentially detrimental effects of glyphosate exposure on human health and provides a platform for future studies.

Additional Information

Publication
Thesis
Language: English
Date: 2020
Keywords
Differentiation, Epigenetics, Gene Expression, Glyphosate, Osteoblast, Proliferation
Subjects
Glyphosate $x Physiological effect
Osteoblasts
Cell physiology

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