C O N T A C T Department of Pathology – Mail Code 7750 The University of Texas Health Science Center 7703 Floyd Curl Drive San Antonio, Texas 78229-3900 INFORMATION Email: abboudwerner@uthscsa.edu Phone: (210) 567-1913   Fax: (210) 567-6729

TEACHING
Renal Pathology Course Instructor, Dental School
Laboratory Instructor, Medical School
Renal Pathology training for residents and fellows


DESCRIPTION OF RESEARCH
Research in my lab has focused on the role of macrophage colony stimulating factor (CSF-1) in osteoclastogenesis. Osteoblasts and stromal cells are the major source of CSF-1 in bone and these cells synthesize the membrane (m) and soluble (s) forms of CSF-1. Both sCSF-1 and mCSF-1 have been shown to support osteoclastogenesis in vitro. The importance of CSF-1 in osteoclastogenesis in vivo has been shown in studies using op/op mice that are deficient in both CSF-1 isoforms. Absence of CSF-1 in op/op mice results in decreased osteoclasts and leads to osteopetrosis and failure of tooth eruption. Injection of recombinant human CSF-1 rescues the osteopetrotic defect in op/op mice, however, relapse occurs one month after therapy. The goal of our studies has been to determine the effect of sCSF-1 and mCSF-1 on osteoclastogenesis in vivo. Using a transgenic approach, we have demonstrated that selective expression of either sCSF-1 or mCSF-1 in osteoblasts of op/op mice using the osteocalcin promoter rescued the osteopetrotic defect. These findings indicate that either isoform is sufficient for osteoclastogenesis in vivo. In these studies, teeth in op/op mice expressing mCSF-1 erupted and showed an amelogenesis imperfecta-like phenotype. This has lead to work designed to elucidate the biologic effect CSF-1 on tooth matrix formation. Our lab has also focused on identifying regulatory elements in the CSF-1 promoter that control its expression in tissues. During embryogenesis and postnatally, CSF-1 is expressed in a tissue-specific manner; however, the cis-acting elements that control CSF-1 gene expression in the cell types that comprise these tissues is unknown. To identify these cis-acting elements, in vitro and in vivo studies using lacZ transgenic mice are being performed. Mice containing fragments of the CSF-1 promoter linked to lacZ have been generated and the temporal and spacial pattern of lacZ expression during embryogenesis and postnatally are being evaluated. These projects are supported through VA Merit and NIH funding.


SELECTED PUBLICATIONS
1. Abboud SL, Bunegin M, Ghosh-Choudhury N, Woodruff K: Analysis of the mouse CSF-1 gene promoter in a transgenic mouse model. J Histochem Cytochem 51:941-949, 2003.
2. Abboud SL, Liu C, Shen V, Ghosh-Choudhury N, Woodruff K: Osteoblast-specific targeting of soluble colony-stimulating factor-1 increases cortical bone thickness in mice. J Bone Min Res 18: 1386-1394, 2003.
3. Bsoul S, Terezhalmy G, Abboud H, Woodruff K, Abboud SL: PDGF BB and bFGF stimulate DNA synthesis and upregulate CSF-1 and MCP-1 gene expression in dental follicle cells. Arch Oral Biol 48:459-465, 2003.
4. Abboud SL, Woodruff K, Liu C, Shen V, Ghosh-Choudhury N: Rescue of the osteopetrotic defect in op/op mice by osteoblast-specific targeting of soluble colony stimulating factor-1 (CSF-1). Endocrinology 143:1942-1949, 2002.
5. Abboud SL, Haile DJ: A novel iron-regulated protein that exports iron from mammalian cells. J Biol Chem 275:19906-19912, 2000.
6. Feliers D, Woodruff K, Abboud S: Potential role of insulin-like growth factor binding protein-4 in the uncoupling of bone turnover in multiple myeloma. Brit J Haematol 104, 1999.
7. Abboud SL, Woodruff KA, Ghosh Choudhury G: Retroviral-mediated gene transfer of CSF-1 into op/op stromal cells to correct defective in vitro osteoclastogenesis. J Cell Physiol 176:323-331, 1998.

Updated on 08/06/2004