Articular cartilage is found at the articulating ends of bones in the synovial joint. It is an important load-bearing tissue that is essential for normal joint function. Due to its intrinsically poor repair potential, injuries to articular cartilage do not heal and clinical intervention is required. Tissue-engineered cartilage has emerged as an attractive alternative treatment option for large cartilage lesions. For these tissue-engineered grafts to succeed in vivo, the integration of the graft with the host tissue is crucial, especially at the osteochondral interface. Currently the mechanisms underlying the formation and maintenance of the osteochondral interface are not well understood.

The objective of this thesis is to test the hypothesis that heterotypic cellular interaction plays an important regulatory role in the formation and homeostasis of the osteochondral interface, especially for tissue engineered osteochondral grafts. We first examined the interactions between chondrocytes and osteoblasts in a novel co-culture model and then on a multiphasic osteochondral construct in order to form distinct yet continuous regions of cartilage, interface, and bone. We found that chondrocytes and osteoblasts were able to maintain their specific phenotype in co-culture. Chondrocytes produced a glycosaminoglycan-rich cartilage matrix and osteoblasts were found to synthesize a collagen matrix predominantly consisting of type I collagen. Furthermore, we evaluated the effects of cellular interactions between subpopulations of chondrocytes on the maintenance of the osteochondral interface using both 2-D and 3-D co-culture models. We found that surface zone chondrocytes regulated deep zone chondrocyte mineralization and this process was found to be mediated by PTHrP. Finally, the relevance of these cellular interactions in the context of tissue engineering of an integrative osteochondral graft will be discussed.