Document Detail


Osteoblast-specific overexpression of human interleukin-7 rescues the bone mass phenotype of interleukin-7-deficient female mice.
MedLine Citation:
PMID:  22258693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Hector L Aguila; Se Hwan Mun; Judith Kalinowski; Douglas J Adams; Joseph A Lorenzo; Sun-Kyeong Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  27     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-09-27     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1030-42     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Society for Bone and Mineral Research.
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MeSH Terms
Descriptor/Qualifier:
Animals
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Expression Regulation*
Humans
Interleukin-7 / deficiency*,  genetics*
Lymphopoiesis
Mice
Mice, Knockout
Mice, Transgenic
Osteoblasts / metabolism*
Phenotype
Polymerase Chain Reaction
Rats
Sex Factors
Grant Support
ID/Acronym/Agency:
R01 AR055143/AR/NIAMS NIH HHS; R01 AR055143-02/AR/NIAMS NIH HHS; R01-AR048714/AR/NIAMS NIH HHS; R01-AR055143/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-7
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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