Date of Award

Fall 12-20-2022

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Jessica Cottrell, Ph.D.

Committee Member

Daniel Brian Nichols, Ph.D.

Committee Member

Constantine Bitsaktsis, Ph.D.

Keywords

Manganese chloride, chondrogenesis, chondrocyte, hypertrophic cartilage, endochondral ossification, osteoarthritis

Abstract

Manganese is an essential trace element found in humans, which aids in several processes including brain and nerve function, glucose metabolism, calcium absorption, and bone formation and homeostasis. Specifically, bone homeostasis utilizes osteoblasts and osteoclasts, cells which function to build and reabsorb bone respectively, as well as chondrocytes, cells which aid in endochondral ossification. Chondrocytes deposit extracellular matrix components, such as aggrecan, collagen, and proteoglycans, that provide the necessary scaffold for osteoblasts to synthesize and mineralize bone. Activation of the rapamycin (mTOR) pathway influences the regulation of several cellular processes, such as skeletal development and bone homeostasis. In this study, it was hypothesized that Manganese Chloride (MnCl2) treatments would activate the RHEB/mTOR pathway in the murine ATDC5 cell line to enhance chondrocyte maturation and protection against degradation. To test this hypothesis, the effects of MnCl2 treated ATDC5 cells were measured through cellular proliferation, alkaline phosphatase activity, calcium deposition, proteoglycan concentrations, and gene expression at timepoints. Our results found that MnCl2 dose dependently decreased chondrocyte proliferation and proteoglycan deposition, while increasing alkaline phosphatase activity and calcium deposition.

Additional Files
Somera - Committee Signature PageN.pdf (672 kB)
Committee Approval Sheet
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