Research Interests

Our research interests revolve around the formation, maintenance, diseases and repair of bones and muscles. Our laboratory is pursuing research problems in three areas:

• Limb development and skeletal patterning.
• The roles of retinoids (vitamin A derivatives) in regulating cell and tissue function.
• Microgravity effects on musculoskeletal tissues in embryos and adults.

Our studies of limb development currently focus on the role of retinoic acid and its metabolism in establishing and modifying the pattern of skeletal development in the growing limb bud. Our NIH supported work in this area focuses on chick embryos and involves in vivo microsurgery and grafting studies, tissue culture models of cell and tissue differentiation and metabolism, and molecular biologic approaches to understanding the roles of various gene products in differentiation, patterning and metabolism.

Our interest in retinoids is focused on our limb development studies as described above, involving HPLC fractionation and scintillation counting to trace the metabolism of retinoic acid by cells from various regions of the chick limb. We are also using in situ hybridization to map developmental changes in the distribution of retinoid binding proteins in the developing limb, and recombinant DNA/eukaryotic expression vectors to examine the roles of some of these proteins in retinoid metabolism. Preliminary studies are underway to begin extending our analyses of retinoid metaboism to better understand the reduction of vitamin A levels in patients with AIDS.

In a recently funded collaboration with Dr. Brenda Klement, we will be exploring the effects of microgravity on nutrient flow through the cartilage matrix to the cartilage cells (chondrocytes) that normally maintain it. In normal gravity conditions, joint cartilages undergo cyclic compression and decompression with use. During compression, fluid is squeezed out into the joint cavity where it picks up oxygen and nutrients and releases wastes. During decompression, the refreshed fluid is reabsorbed into the viscous cartilage matrix. In the absence of gravity, compression and decompression naturally play less of a role in nutrient, oxygen and waste exchange. Under these conditions, factors affecting diffusion and flow take on greater importance in nourishing the chondrocytes than they do on earth. This project will be carried out with the assistance of NASA scientists at the NASA/Glenn Research Center in Cleveland OH and will first involve developing an apparatus for studying nutrient flow.

Relevant Publications

von Deutsch, D.A., Abukhalaf, I.K., Wineski, L.E., Aboul-Enein, H., Paulsen, D.F., and Potter, D.E. Distribution and muscle-sparing effects of clenbuterol in hindlimb-suspended rats. Pharmacology 2002; 65:38-48.

Wineski, L.E., von Deutsch, D.A., Abukhalaf, I.K., Pitts, S.A., Potter, D.E., Paulsen, D.F. Muscle-specific effects of hindlimb suspension and clenbuterol in mature male rats. Cells Tissues Organs, 2002;171:188-198.

Abukhalaf, I.K., von Deutsch, D.A., Wineski, L.E., Parks, B., Paulsen, D.F., Aboul-Enein, H., Potter, D.E. Quantitation of clenbuterol in biological matrices using GC-MS and EIA. Biomedical Chromatography 2000;14:99-105.

von Deutsch, D.A., Abukhalaf, I.K., Wineski, L.E., Aboul-Enein, H.Y., Pitts, S.A., Parks, B.A., Oster, R., Paulsen D.F., and Potter, D.E. ß-Agonist-induced alterations in organ weights and protein content: Comparison of racemic clenbuterol and its enantiomers. Chirality 2000;12:637-48.

Paulsen, D.F. Retinoic acid and limb-bud outgrowth: Review and hypothesis. Anatomy
and Embryology 1994; 190: 399-415.

Keywords

Limb bud, Cartilage, Embryology, Bone Histology, Muscle, Vitamin A, Chondrogenesis, Retinoids, Connective tissue, Muscle, Bone, Atrophy, beta-Adrenergic agents, Microgravity.