Date of Graduation

5-2021

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Tian, Z. Ryan

Committee Member

Epstein, Joshua

Second Committee Member

Fan, Chenguang

Third Committee Member

Yaccoby, Shmuel

Fourth Committee Member

Huang, Yan

Keywords

Osteoblasts; Tumor oncogenes; Osteoclasts; Cell proliferation; Tumor growth suppression; Antioxidant pathway; Bone density; Bone deterioration

Abstract

Expansion of plasma cells within the bone marrow constitutes the onset of multiple myeloma (MM). This disease manifests clinically primarily through the formation of osteolytic bone lesions that can lead to osteoporosis. The reason for the development of such lesions is the disruption of the equilibrium between bone resorption and bone formation as a result of proliferation of osteoclasts and reduction in the number of osteoblasts in the process of differentiation of mesenchymal stem cells (MSCs). The maintenance of bone architecture is critically dependent on osteoblasts and osteoclasts, the activity of which is underpinned by a range of soluble factors. The present study sought to reduce cellular genotoxicity by using t-BHQ to target the major antioxidant gene heme-oxygenase 1 (HMOX1).

This study provides a detailed investigation of the function of osteoclasts, osteoblasts MSCs and reactive oxygen species ROS in MM, especially with regards to disease progression. Since MM is associated with downregulation of HMOX1 expression, this study postulates that t-BHQ could be used to pharmacologically upregulate the expression of HMOX1. This pharmacological agent t-BHQ can trigger apoptosis in MM, confer cell protection against oxidative damage by upregulating HEME OXYGENASE 1, prevent osteoclasts from forming and ultimately avoid bone deterioration.

Student’s two-tailed t-test was conducted to determine how the different types of cells (MM cell lines, MSCs, osteoblasts and osteoclasts) responded to t-BHQ. The P-value was less than 0.05, signifying that the results were of statistical significance.

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