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My students and I work with research scientists at the University of Massachusetts Medical School and the University of Southern California Medical School to study bone biology. Bone mass is dependent on osteoclasts that resorb bone, and osteoblasts that build new bone. Recent work has focused on the discovery of new potential molecular targets for bone loss drug therapy. Using a modern biotechnology approach, we combine bioinformatics of the human genome project with micro-chip/gene array technology, RNAi, and other technologies to identify targets and test them for physiological relevance during osteoclast differentiation. Using these methods, we have identified several new genes that function during osteoclastogenesis. Two membrane proteins, OGR-1 and OCS were highly expressed during osteoclast differentiation in vivo during rat and mouse bone development and in vitro. Inhibition by either RNAi or antibodies demonstrated that these gene products were required for optimal osteoclast differentiation. Studies are underway to determine if these two genes might be targets for therapies (antibodies, RNAi, or small molecules) designed to down-regulate osteoclast function and combat bone loss in vivo. Identification and study of other new potential osteoclast target molecules are ongoing.
Using Biotechnology to Identify New Potential Targets for Bone Loss Drug Therapy
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