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Publication : Osteoblast-specific overexpression of human interleukin-7 rescues the bone mass phenotype of interleukin-7-deficient female mice.

First Author  Aguila HL Year  2012
Journal  J Bone Miner Res Volume  27
Issue  5 Pages  1030-42
PubMed ID  22258693 Mgi Jnum  J:233279
Mgi Id  MGI:5781075 Doi  10.1002/jbmr.1553
Citation  Aguila HL, et al. (2012) Osteoblast-specific overexpression of human interleukin-7 rescues the bone mass phenotype of interleukin-7-deficient female mice. J Bone Miner Res 27(5):1030-42
abstractText  Interleukin-7 is a critical cytokine for lymphoid development and a direct inhibitor of in vitro osteoclastogenesis in murine bone marrow cultures. To explore the role of IL-7 in bone, we generated transgenic mouse lines bearing the 2.3-kb rat collagen 1alpha1 promoter driving the expression of human IL-7 specifically in osteoblasts. In addition, we crossed these mice with IL-7-deficient mice to determine if the alterations in lymphopoiesis, bone mass, and osteoclast formation observed in the IL-7 knockout (KO) mice could be rescued by osteoblast-specific overexpression of IL-7. Here, we show that mice overexpressing human IL-7 in the osteoblast lineage showed increased trabecular bone volume in vivo by microCT and decreased osteoclast formation in vitro. Furthermore, targeted overexpression of IL-7 in osteoblasts rescued the osteopenic bone phenotype and B-cell development of IL-7 KO mice but did not have an effect on T lymphopoiesis, which occurs in the periphery. The bone phenotypes in IL-7 KO mice and targeted IL-7-overexpressing mouse models were observed only in females. These results likely reflect both direct inhibitory effects of IL-7 on osteoclastogenesis in vivo and sex-specific differences in responses to IL-7.
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