Articular cartilage is a connective tissue that facilitates motion in healthy joints. When mature cartilage undergoes degeneration, the endogenous chondrocytes do not repair the extracellular matrix. This necessitates surgical interventions such as the transplantation of additional chondrocytes to aid in repair. The general motivation of this dissertation was to contribute to the understanding of the cellular and molecular responses of chondrocytes to the mechanical environment encountered in cartilage repair situations.

In vitro culture systems were used to simulate and study some of the situations in which chondrocytes participate in cartilage repair. The presence of an appropriate number of reparative cells in an articular cartilage defect is probably important for consistently successful repair. Transplanted chondrocytes were found to proliferate markedly after coming into contact with healthy cartilage. The rate of DNA synthesis was inhibited by the application of static compressive load, suggesting that proliferation of such chondrocytes would be extremely sensitive to regulation by the in vivo mechanical environment.

Static and dynamic compression had differential effects on chondrocytes within their native cartilage matrix that varied with the growth stage of the cartilage tissue. Static loading inhibited both cell proliferation and matrix biosynthesis regardless of the age of the donor animal. In contrast, dynamic loading stimulated matrix biosynthesis only in the cartilage of newborn animals. Thus, the synthesis of matrix and DNA, two processes involved in cartilage repair, are regulated independently by mechanical loading.

In vitro studies also explored the molecular basis for mechanical regulation of newborn chondrocytes. Activation of extracellular signal-regulated kinase (ERK) is an early event in the regulation of chondrocytes by various chemical and mechanical stimuli. The ERK activation responses of chondrocytes to serum and interleukin-1 in various in vitro models indicated that regulation of ERK was modulated, in part, by the degree of chondrocyte exposure to an extensive cartilage matrix. Furthermore, when cartilage explants from newborn animals were exposed to dynamic compressive loads, ERK activity was elevated for a sustained period of time.

Taken together, the above studies demonstrate that mechanical stimuli can modulate a number of cellular and molecular processes that are critical for chondrocyte-mediated cartilage repair.