Exploration of the Role of Indian Hedgehog Signaling in PCB Toxicity on Skeletal Bone

Publication Date

July 2019

Location

LSU Health Medical Education Building

Document Type

Abstract

Start Date

26-7-2019 9:00 AM

End Date

26-7-2019 12:00 PM

Description

Polychlorinated Biphenyl (PCB) is a toxic chemical commonly used in electrical equipment. Consumption of PCB through bioaccumulation leads to adverse health risks like carcinogenesis in humans. In recent experimental studies performed on rats in our lab, showed that bone health in PCB-126 exposed animals were compromised. Compared to rats in the control group, rats treated with PCB had an overall smaller tibia bone size. In a related experiment, our lab was able to show that there is some protection from PCBs toxic effects on the bone in Aryl Hydrocarbon Receptor (AHR) knockout rats. This data provided more evidence that PCB acts through this receptor. However, the signaling pathway leading to bone toxicity is still unclear. To further investigate how exactly PCB may be affecting bone growth, RNA sequencing was done. Interestingly, Indian Hedgehog (IHH) is one of the genes that is drastically upregulated in wild type rats treated with PCB, but not in AHR knock out rats. Given that IHH plays an important role in bone growth and elongation, we hypothesize that IHH signaling is perturbed by PCB effects on bone growth. By performing real time PCR experiments on rat bone samples, we expect to see amplification of IHH verifying the upregulation of the gene seen in the RNA sequencing data results. We will further investigate IHH signaling in the marrow and shaft. With this information, more can be done to understand the role of IHH on the bone.

Comments

Mentor: Martin Ronis

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Jul 26th, 9:00 AM Jul 26th, 12:00 PM

Exploration of the Role of Indian Hedgehog Signaling in PCB Toxicity on Skeletal Bone

LSU Health Medical Education Building

Polychlorinated Biphenyl (PCB) is a toxic chemical commonly used in electrical equipment. Consumption of PCB through bioaccumulation leads to adverse health risks like carcinogenesis in humans. In recent experimental studies performed on rats in our lab, showed that bone health in PCB-126 exposed animals were compromised. Compared to rats in the control group, rats treated with PCB had an overall smaller tibia bone size. In a related experiment, our lab was able to show that there is some protection from PCBs toxic effects on the bone in Aryl Hydrocarbon Receptor (AHR) knockout rats. This data provided more evidence that PCB acts through this receptor. However, the signaling pathway leading to bone toxicity is still unclear. To further investigate how exactly PCB may be affecting bone growth, RNA sequencing was done. Interestingly, Indian Hedgehog (IHH) is one of the genes that is drastically upregulated in wild type rats treated with PCB, but not in AHR knock out rats. Given that IHH plays an important role in bone growth and elongation, we hypothesize that IHH signaling is perturbed by PCB effects on bone growth. By performing real time PCR experiments on rat bone samples, we expect to see amplification of IHH verifying the upregulation of the gene seen in the RNA sequencing data results. We will further investigate IHH signaling in the marrow and shaft. With this information, more can be done to understand the role of IHH on the bone.