Washington University in St. Louis
Campus Box 1137
One Brookings Drive
St. Louis, MO 63130-4899
My research interests are in bone cell biology. Bone is a dynamic tissue that is continually remodeled and renewed throughout life, and it serves as a structural framework for the body, physiological reservoir for minerals, and the birthplace of hematopoietic cells in the marrow. To fulfill these functions, the activities of bone-degrading osteoclasts and bone-forming osteoblasts are normally precisely balanced. However, this homeostasis is disturbed in diseases such as osteoporosis, osteopetrosis, Paget's, rheumatoid arthritis, periodontal disease, or certain cancers, and the consequent effects can be severe to life-threatening.
We are particularly interested in the osteoclast (Oc)-related phase of this coupled bone resorption/formation process and have been studying how Oc form within bone, what special attributes of an Oc enable only this cell type to resorb bone, and what circulating or local signals control Oc development, function, and survival. Recently, we have focused on how endothelial cells lining the vasculature of bone directly regulate Oc formation and resorption through their expression of cell-associated and soluble signals. Our goal is to learn how precursor cells in the circulation become attracted to and migrate through blood vessels to give rise to Oc within bone, what signals initiate or mediate this, and what determines how many Oc will form or where bone will be resorbed and rebuilt in normal and disease states. Our work indicates that certain cytokines, chemokines, free radicals, cell adhesion molecules, proteolytic enzymes, and other specific signaling molecules are important in these events. This research is being conducted in collaboration with Dr. Philip Osdoby in Biology and employs a wide variety of tissue culture, immunological, microscopic, biochemical, molecular, and functional (resorption) assays.
Photo caption: Section of human bone stained with the antibody RANKL to show that activated vascular endothelial cells and bone-forming osteoblasts express this important regulatory molecule responsible for causing the formation of bone-resorbing osteoclasts.
Formigli, L., Orlandini, S., Benvenuti, S., Masi, L., Pinto, A., Gattei, V., Bernabei, P., Robey, P., Collin-Osdoby, P., and M. Brandi. (1995) In vitro structural and functional relationships between preosteoclastic and bone endothelial cells: A juxtacrine model for migration and adhesion of osteoclast precursors. J. Cell. Physiol. 162:199-212.
Sunyer, T., Lewis, J., Collin-Osdoby, P., and P. Osdoby. (1999) Estrogen's bone protective effects may involve differential IL-1 receptor regulation in human osteoclast-like cells. J. Clin. Investig. 103:1409-1418.
Collin-Osdoby, P., Rothe, L., Bekker, S., Anderson, F., and P. Osdoby. (2000) Decreased nitric oxide levels stimulate osteoclastogenesis and bone resorption both in vitro and in vivo on the chick chorioallantoic membrane in association with neoangiogenesis. J. Bone Miner. Res. 15:474-488.
Collin-Osdoby, P., Rothe, L., Anderson, F., Nelson, M., Maloney, W., and P. Osdoby. (2001) Receptor activator of NF-kB ligand and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis. J. Biol. Chem. 276: 20659-20672.
Collin-Osdoby, P., Rothe, L., Anderson, F., Nelson, M., Maloney, W., and P. Osdoby. (2002) Basic fibroblast growth factor stimulates osteoclast recruitment, development, and bone pit resorption in association with angiogenesis in vivo on the chick chorioallantoic membrane and activates isolated avian osteoclast resorption in vitro. J Bone Miner Res. 17: In press.
Yu, X., Collin-Osdoby, P., and P. Osdoby. (2002) SDF-1 increases recruitment of osteoclast precursors by upregulation of matrix metalloproteinase-9 (MMP-9) activity. Connec. Tiss. Res. In press.