Mechanism of Bone Growth and Repair: Despite decades of study, the mechanism by which a thin layer of cartilage, the epiphyseal growth plate, regulates long bone growth remains poorly understood. Our earlier observation that the oxygen tension is a potent regulator of chondrocyte activity and mediated by the oxygen sensitive transcription factor, HIF-1, provided a new understanding of the regulatory process. The recent finding that HIF-2 is required for chondrocyte maturation and that it serves to regulate a previously unrecognized step in the maturation pathway, autophagy, holds promise of providing new insights into phase co-ordination that is especially relevant to the growth process. Our ongoing studies are directed at examining the impact of these proteins on the maturation, the extent of hypertrophy and the induction of chondrocyte mineralization and apoptosis, as well as promoting the proliferation of new cells into the maturation cascade.

Tissue Engineering of the Intervertebral Disc: Back pain, a significant source of morbidity in our society, is directly related to the pathology of the degenerate intervertebral disc. At present, the treatment of degenerative disc disease consists of therapies that are aimed at symptomatic relief. However, recent advances in the understanding of tissue repair and stem cell biology indicates that it may be possible to rebuild diseased or degenerate tissues using endogenous stem cells. The goal of our investigation is to characterize disc progenitor cells (DPC) from both normal and diseased discs. Then, to define the environmental conditions that enhance DPC differentiation into cells that exhibit the phenotypic characteristics of the inner tissue, the nucleus pulposus. Experiments are in progress to repopulate the disc in vivo by promoting the recruitment and differentiation of these endogenous stem cells.

Creating Bioactive Surfaces for Repair of Fractured and Infected Bone: The aim of this work is to develop a new generation of smart implants that promote osteogenesis and prevent bacterial infection. This study relies heavily on the development of new chemical techniques to generate linkages between metals and bioactive molecules and uses imaging techniques such as micro-tomography light, electron and X-ray imaging to evaluate efficacy of healing.

Apoptosis; autophagy; Arthritis; Biochemistry; Biomineralization; Bone; Cartilage; Growth Plate; Matrix Vesicles; Intervertebral disc, Annulus Fibrosus; HIF; Nucleus Pulposus; Orthopedics; Surgery; Tissue Engineering