The long term objective is to define the molecular mechanisms responsible for vascular invasion associated with the formation of secondary centers of ossification during long bone growth. The hypothesis to be tested states that vascular invasion of the epiphyseal growth plate is mediated through interactions between specific cartilage matrix components of the hypertrophic zone and invading capillary endothelial cells. These components, termed matrix angiogenic factors (MAF)provide the proper environment for endothelial cells to invade the growth plate. To test this hypothesis, growth properties of endothelial cells (cell adhesion, migration and proliferation) will be compared when endothelial cells are grown on culture dishes coated with either growth cartilage matrix or articular cartilage matrix. The regulation of expression of MAF by cartilage-derived growth factor (fibroblast growth factor) and somatomedin C will also be examined. The effect of cartilage matrix proteoglycans on endothelial attachment will also be examined. Matrices from chondrocyte cultures grown in the presence and absence of these growth factors will be utilized to assess their effect on the growth properties of endothelial cells. Besides the obvious significance of these studies to pediatric orthopedics, the knowledge derived here will further our understanding of vascularization during fracture repair and transplantation.
| Chintala, S K; Miller, R R; McDevitt, C A (1995) Role of heparan sulfate in the terminal differentiation of growth plate chondrocytes. Arch Biochem Biophys 316:227-34 |
| Chintala, S K; Miller, R R; McDevitt, C A (1994) Basic fibroblast growth factor binds to heparan sulfate in the extracellular matrix of rat growth plate chondrocytes. Arch Biochem Biophys 310:180-6 |
| Miller, R R; Rydell, P A (1993) Primary culture of microvascular endothelial cells from canine meniscus. J Orthop Res 11:907-11 |
| Miller, R R; McDevitt, C A (1991) Thrombospondin in ligament, meniscus and intervertebral disc. Biochim Biophys Acta 1115:85-8 |
