Date of Award

Fall 12-4-2017

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Jessica Cottrell, Ph.D.

Committee Member

Daniel Brian Nichols, Ph.D.

Committee Member

Allan Blake, Ph.D.

Committee Member

Angela V. Klaus, Ph.D.

Committee Member

Heping Zhou, Ph.D.

Keywords

chondrocyte, zinc, fracture, insulin, ossification, maturation, regeneration

Abstract

Fracture healing is characterized by inflammation, cartilage formation, bone deposition, and remodeling. Endochondral ossification is an important part of callus formation that relies on the maturation of chondrocytes. Early in their maturation these cells express collagen type II alpha 1 chain (COL2A1) and express collagen type X alpha 1 chain (COL10A1) as they mature further and become hypertrophic chondrocytes. Activation of the insulin pathway is considered a primary factor involved in the initiation of chondrogenesis and its progression during bone healing. Insulin mimetics like zinc chloride (ZnCl2) have been shown to improve bone healing outcomes and enhance bone healing, but the mechanism by which insulin mimetics enhance bone healing is unclear. We hypothesized that treatment of chondrocytes with ZnCl2 would activate Akt within the insulin-signaling pathway and promote chondrocyte maturation and differentiation similar to insulin. The ATDC5 chondrogenic cell line was treated with zinc chloride (ZnCl2) and evaluated for chondrogenesis by measuring calcium deposition, proteoglycan synthesis, protein expression, and gene expression at specific timepoints between 0-28 days. Our data demonstrates that ZnCl2 induces the insulin pathway by phosphorylation of Akt. ZnCl2 treatment promotes chondrogenesis as seen by increased expression of chondrogenic markers COL2A1 and COL10A1 and calcium deposition.

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