Osteoblasts are bone forming cells that are also closely linked to the generation of hematopoietic cells in bone marrow. The microenvironments generated by osteoblastic cells are known to be crucial in development of a variety of stem cell lineages, ranging from the osteoclast precursor stem cell lineage through the development of all immune cells from early hematopoietic stem cells in stromal compartments of marrow. Recent work has demonstrated that the osteoblast stem cell acts as a central cell type in establishing the physical and molecular microenvironments necessary for activation of differentiation pathways in both normal and neoplastic cells, under the influence of hormonal and paracrine messages, which interact through cross-talk between signaling pathways intersecting in the osteoblast. This laboratory has been studying the regulation of osteoblast and osteoclast stem cell differentiation under the influences of hormones and cytokines. Currently we are investigating the interaction among several differentiation-regulating factors (vitamin D metabolites, prolactin, parathyroid hormone, and estrogen) in osteoblast differentiation, as a function of the markers of differentiated functions that these factors induce in treated cells. Future work will elucidate the role of cross-talk in generating cell surface and soluble paracrine signaling factors. We will be using either mouse bone marrow stem cells or isolated circulating human osteoblastic stem cell precursors, in reconstituted in vitro models of stromal environments, to determine the roles of classical hormones, paracrine factors, and electromechanical stress in generation of stem cell descendants expressing markers of lymphoid, monocytic, osteoclastic, classical osteocytic, and/or osteosarcoma cell types. These studies will develop a better understanding of the molecular characteristics of the microenvironments generated by osteoblastic stem cells and the regulation of their properties by external influences.
The overall goal of this laboratory is to examine basic mechanisms of signal transduction, focusing primarily on the mechanisms by which hormones and other regulatory factors act on cells in vitro. The major lines of research now ongoing are:
Studies of hormone responsiveness in bone cells. We have studied multiple systems of hormone response in bone cells. We have characterized the effects of parathyroid hormone, cytokines, other hormones and other agents on adenylate cyclase, protein kinases, ornithine decarboxylase, collagen synthesis and other metabolic activities.
Molecular biology of the cell membrane. We have used molecular biological techniques to investigate signal transduction pathways induced by agents which act at the cell membrane, including studies of hormone receptors, serine-threonine protein kinases, tyrosine protein kinases, and regulation of gene expression by these signal transduction pathways.
Effects of electromagnetic fields on hormone responses. We have studied the interaction of low-energy electromagnetic energy with signal transduction systems in bone cells, breast cancer cells, and leukemia cells. Our findings indicate that alteration of the function of membrane receptors by electromagnetic fields is an important factor in both normal and pathological responses of many biological systems to electromagnetic energy.
See publications on PubMed
Simko, M., Kriehuber, R., Weiss, D.G, and Luben, R.A. The effects of 50 Hz EMF exposure on micronucleus formation and apoptosis in transformed and non-transformed human cell lines. Biolectromagnetics 19:85-91 (1998).
Dibirdik I., Kristupaitis D., Kurosaki T., Tuel-Ahlgren L., Chu A., Pond D., Tuong D., Luben R.A. and Uckun F.M. Stimulation of Src family protein tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase C gamma2 activation in lymphoma B-cells exposed to low energy electromagnetic fields. J. Biol. Chem. 273:4035-4039 (1998).
WHO Working Group on Non-Thermal Effects of RF Radiation (M. Repacholi, Chair; 40 members, including R.A. Luben). Low-level exposure to radiofrequency fields: Health effects and research needs. Bioelectromagnetics 19:1-19 (1998).
Luben, R.A. Effects of microwave radiation on signal transduction processes of cells in vitro. In "Non-Thermal Effects of RF Electromagnetic Fields" J.H. Bernhardt, R. Matthes and M.H. Repacholi, eds. Maerkl-Druck Publishing, Munich, Germany, pp. 101-118 (1997).
National Research Council (National Academy of Sciences) Committee on Possible Effects of Electromagnetic Fields on Biologic Systems (16 Members, including R.A. Luben): "Possible Health Effects of Exposure to Residential Electromagnetic Fields" National Academy Press, Washington (1996).