The goal of this study is to examine the role of Interleukin 7 (IL-7) in the regulation of osteoclast formation in vivo. IL-7 is produced by stromal cells in bone marrow. It is one of the cytokines that enhances early B cell development. Recently, early stage B lineage precursor cell populations were found to contain osteoclast precursors. This findings suggests that factors modulating B cell development also affect osteoclast precursor cell development. My preliminary findings indicate that bone marrow cells from IL-7 deficient mice have increased osteoclast formation in vitro when stimulated with M-CSF and RANKL and that addition of IL- 7 to cultures of wild-type bone marrow cells decreases osteoclast formation. Previous studies using systematically administered IL-7 have demonstrated that this treatment increases bone resorption by stimulating T cells to produce resorptive cytokine. My in vitro results suggests that IL-7 may have direct inhibitory effects. Therefore, I wish to examine the effects of bone specific over-expression of IL-7 in transgenic mice to determine the direct action of this cytokine on osteoclast formation in bone in vivo. The major hypothesis of this grant is that IL-Y regulates osteoclast formation and B cell development by influencing the lineage commitment of a common early precursor cell fo both the lymphocyte and the osteoclast. The major question to be determined is that role does IL-7 play in the osteoclastogenesis. I will: Determine the role of IL-7 in osteoclast precursor cell differentiation using bone specific COL1a13.6 and 2.3 promoter-driven IL-7 over- expressing mice. a. I will examine if there is a change in bone mass, osteoblast and osteoblast number as well as bone formation in T and Tg IL-7 using micro-CT, static and dynamic histomorphometric analysis. b. I will examine if there is a change in osteoclast precursor cell number and osteoclastogenesis in vitro in the bone marrow of Tg IL-7 mice compared to WT. c. I will examine bone formation markers in these animals.
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