Graduation Date

Summer 8-18-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Genetics, Cell Biology & Anatomy

First Advisor

Andrew T. Dudley

Abstract

Articular cartilage is a smooth, visco-elastic, aneural, avascular tissue made of water, an exquisitely organized framework of proteoglycans, glycosaminoglycans, and collagen fibrils and articular chondrocytes. It’s beautiful organization and composition provide it with the flexibility and strength to cover, protect and lubricate the ends of long bones in a diarthrodial joint. Cartilage homeostasis relies on articular chondrocytes to translate the mechanical forces of daily activity into efficient remodeling of the extracellular matrix. Age, joint injury, or other insulting factors can progressively incapacitate articular chondrocytes, resulting in cartilage lesions that devolve to degenerative joint disease. Therefore, the central idea explored in this dissertation is the changing chondrogenic potential of articular chondrocytes. In the first study, we asked if chondrogenic potential affects how primary articular chondrocytes respond to dynamic Ca2+ signaling, the primary signaling mediator of mechanotransduction during extracellular matrix remodeling. In the second study, we explored how age and culture conditions that alter chondrogenic potential influence the transcriptional profile of primary articular chondrocytes using in-depth RNA-sequencing technology. These studies highlight that the chondrogenic potential of articular chondrocytes, which is affected by age and the gradual changes in matrix composition, can be understood through dynamic signaling and transcriptional networks and enhanced through tissue engineering principles to improve upon the long-term efficacies of cartilage resurfacing procedures.

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