Exploring ERK1/2 influence on BMP signaling in skeletogenesis of CFP1 knockout cells
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Abstract
Epigenetics provides a possible explanation for the often-observed difference between genotype and the final phenotype. Epigenetics is regulated through a variety of means such as histone methylation. The focus of this paper is on the transcription factor CFP1 and its affects on cell signaling within bone growth and differentiation. CFP1 has been shown to regulate DNA and histone methylation, which affects gene expression. Epigenetics within bone development has been linked to numerous disorders and thus any insights into the underlying mechanisms may help lead to therapeutic solutions. With two primary forms of skeletogenesis, endochondral and intramembranous ossification, three different cell lines were utilized in this paper; each of these representing different stages of differentiation within skeletogenesis. This thesis’ focuses on studying the interaction of two of the primary cell signaling pathways that regulate skeletogenesis, FGF and BMP. The ERK MAPK pathway is one of the FGF signaling pathways that has been shown to previously interact with BMP. Results showed in CFP1 knockout cells that there was a decrease in BMP signaling while there was an increase in the phosphorylation of ERK, the final step in ERK MAPK pathway. In order to possibly restore BMP signaling, inhibitors of the phosphorylation of ERK were utilized. Through Western Blot analysis, BMP signaling could be raised with inhibition of ERK demonstrating the antagonistic relationship between them. It appears that CFP1 has an overall inhibitory role in the ERK MAPK pathway, and that when it has been removed there is a decrease in BMP signaling, which can affect proper bone growth and differentiation.
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2024