title: Osteoblast-specific overexpression of human interleukin-7 rescues the bone mass phenotype of interleukin-7-deficient female mice.
abstract: 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 1α1 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 µCT 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.
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030-1601, USA. aguila@nso1.uchc.edu
authors.forename: Hector L
authors.initials: HL
authors.lastname: Aguila
authors.forename: Se Hwan
authors.initials: SH
authors.lastname: Mun
authors.forename: Judith
authors.initials: J
authors.lastname: Kalinowski
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lorenzo
authors.forename: Sun-Kyeong
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D015851:Interleukin-7 / Q000172:deficiency* / Q000235:genetics*; D038041:Lymphopoiesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D012737:Sex Factors
chemical_list: D015851:Interleukin-7