Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Frank Beier

Second Advisor

Dr. David Hess

Third Advisor

Dr. Chris Pin

Abstract

Osteoarthritis is a multifactorial disease that is characterized by cartilage degeneration. Manipulation of cells to form cartilage has been considered as a potential form of therapy, but currently there are no feasible molecular candidates. Recently this lab has identified four pharmacological compounds that could promote cartilage formation. We hypothesized that combinations of manuymycin A, PP2, Y27632, and cGMP would promote chondrogenesis more efficiently than individual compounds. Through fluorescent cytoskeleton imaging, toluidine blue staining, and real-time PCR, this study demonstrated that Manumycin A and cGMP had no effect on most tested parameters in ATDC5 cells. However, Y27632 caused significant changes in gene expression and PP2 negative affected glycosaminoglycan synthesis of ATDC5 chondrogenesis. Making them unsuitable for the intended promotion of articular cartilage generation. In summary, this study was not able to identify a compound, or combination of compounds that was able to successfully promote chondrogenesis without undesired effects.

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