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The Divieti-Pajevic Laboratory studies the role of PTH and Gs-alpha in osteocytes by using in vivo mouse models in which the PTH/PTHrp receptor and Gs-alpha can be specifically ablated. In addition, the lab has in vitro models in which we are studying the effect of microgravity on osteocyte functions.
Although it is well established that bone responds to its mechanical environment, the mechanisms underlying the mechanotransduction pathway are poorly understood. Osteocytes are the most abundant cells in bone, but their relative inaccessibility and (until recently) the lack of good in vitro cell models have hampered progress in understanding their roles. Recent evidence points to a mechanosensory function whereby osteocytes regulate bone modeling and remodeling in response to shear or strain forces. Their possible role in calcium and phosphate homeostasis is less clear. Recent work indicates that the ablation of osteocytes in vivo leads to the development of osteoporosis, suggesting that these cells are also involved in normal bone development and/or remodeling.
We have recently established transgenic mice in which the expression of the bacteriophage Cre recombinase is under the control of the promoter for dentin matrix protein-1 (DMP1), a protein expressed exclusively in osteocytes. The main interest of my group is to specifically ablate PPR and Gs-alpha in osteocytes by mating these mice with mice in which the PPR gene is flanked by lox-P sites. Use actions of these models promises to greatly enhance understanding of PTH and Gs-alpha in osteocytes and possibly lead to the development of novel therapeutic agents for osteoporosis or other osteopenic diseases.
In addition, we are interested in establishing a conditionally immortalized osteocytic cell line that fully recapitulates the hallmarks of an osteocyte in vivo by isolating cells from the calvarial and long bones of mice carrying an immortalized Large T-Antigen (SV40-TAg) and expressing green fluorescent protein (GFP) under the control of an osteocyte-specific promoter (8Kb-Dentin Matrix Protein 1- DMP1).
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Endocrine Unit Research Laboratories
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