Date of Award

2007

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Andrew Leask

Second Advisor

Dr. Frank Beier

Abstract

Connective tissue growth factor (CTGF, CCN2) is expressed by mesenchymal cells during development. Mice genetically deficient in CCN2 display severe bone defects and die immediately after birth. The molecular basis of this defect is not known. We've used in vitro models of chondrogenesis to show that CCN2 expression is induced during chondrogenesis, paralleling induction of known early chondrogenic markers (sox9, sox6, l-sox5, type II collagen, aggrecan, decorin and link protein). Real-Time PCR, Western blot and Immunofluorescence reveal that CCN2 is required for the early stages of chondrogenesis, including expression of sox6 and aggrecan, but not type II collagen. Furthermore, focal adhesion kinase (FAK) was found to be an upstream mediator of CCN2 expression and the absence of FAK promotes the process of chondrogenesis. Therefore, CCN2 is required for early chondrogenic events, downstream of FAK and is responsible for regulating components of the chondrogenic extracellular matrix.

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