(Taken from the application): Osteoblast-specific tyrosine phosphatase in osteoblasts. We have recently identified a receptor-like tyrosine phosphatase (osteotesticular protein tyrosine phosphatase, OST-PTP, (Mauro et al, 1994) that has a unique tissue distribution in that it is expressed only in osteoblasts and testes. The extra-cellular receptor domain of OST-PTP has ten fibronectin type III-like repeats suggesting it functions; as an adhesion molecule. We have also shown that OST-PTP mRNA expression is regulated during osteoblast development, with peak of mRNA expression paralleling the peak of the differentiation stage. Finally, we have shown that the levels of OST-PTP are regulated by parathyroid hormone, a key modulator of calcium homeostasis and bone remodeling. These findings have led us to hypothesize that OST-PTP is a key modulator of osteoblast proliferation, differentiation. and mineralization. We propose that OST-PTP can regulate osteoblast function by altering key signal transduction pathways through de-phosphorolation of specific substrates. We also hypothesize that OST-PTP may exert this regulation of osteoblast development by altering the mitogen activated protein kinase (MAPK) pathway. Since glucocorticoids regulate osteoblasts development via the MAP kinase pathway, we further hypothesize that OST-PTP may be an integral part of this signaling cascade. The validation of these hypotheses would demonstrate the existence of a novel signal transduction pathway, specific to osteoblasts, which provides a potential mechanism for the external environment to modulate osteoblast development. This information is critical to the understanding of osteoblast development and the identification of potential molecular targets for future drug design for treatment of bone diseases such as osteoporosis.
| Gugala, Z; Olmsted-Davis, E A; Gannon, F H et al. (2003) Osteoinduction by ex vivo adenovirus-mediated BMP2 delivery is independent of cell type. Gene Ther 10:1289-96 |
| Olmsted-Davis, Elizabeth A; Gugala, Zbigniew; Camargo, Fernando et al. (2003) Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A 100:15877-82 |
| Olmsted-Davis, Elizabeth A; Gugala, Zbigniew; Gannon, Francis H et al. (2002) Use of a chimeric adenovirus vector enhances BMP2 production and bone formation. Hum Gene Ther 13:1337-47 |
