IGF-I increases markers of osteoblastic activity and reduces bone resorption via osteoprotegerin and RANK-ligand

Journal of Translational Medicine

Inma Castilla-Cortázar²  Arancha R de Gortázar¹  Luis F de Castro¹  Jose L Lavandera²  Juan E Puche²  Maria C Sádaba²  Lucia Guerra-Menéndez² 

[1] Department of Histology, Universidad CEU San Pablo, Institute of Applied Molecular Medicine (IMMA), School of Medicine, Madrid, Spain;Department of Medical Physiology, Universidad CEU San Pablo, Institute of Applied Molecular Medicine (IMMA), School of Medicine, Room D-201. C/ Boadilla del Monte s/n, km 5,3, 28668 Madrid, Spain

关键词: IGFBP-5;    IGFBP-4;    RANKL;    Parathormone;    Osteoprotegerin;    Osteocalcin;    Gene expression;    Bone metabolism;    GH;    IGF-I;   

Others  :  824832
DOI  :  10.1186/1479-5876-11-271

 received in 2013-07-31, accepted in 2013-10-16,  发布年份 2013

【 摘 要 】

Background

Bone is one of the major target tissues for Insulin-like Growth Factor I (IGF-I). Low doses of IGF-I were able to improve liver-associated osteopenia. In the present work, a model of partial IGF-I deficiency was used in order to provide insight into the mechanisms of the beneficial actions of IGF-I replacement therapy in bone.

Methods

Several proteins involved in osteoblastic/osteocyte and osteoclastic differentiation and activity were studied in the three experimental groups: control (CO) group (wild type mice, Igf^+/+, n = 10), heterozygous Igf^+/- group with partial IGF-I deficiency (Hz, n = 10), and heterozygous Igf^+/- mice treated with IGF-I for 10 days (Hz + IGF-I, n = 10).

Results

Data in this paper confirm that the simple partial IGF-I deficiency is responsible for osteopenia, determined by densitometry and histopathology. These findings are associated with a reduced gene expression of osteoprotegerin, sclerostin, calcitonin receptor (CTR), insulin-like growth factor binding protein 5 and RUNX2. IGF-I replacement therapy normalized CTR gene expression and reduced markers of osteoclastic activity.

Conclusions

Low doses of IGF-I constituted a real replacement therapy that normalized IGF-I serum levels improving the expression of most of these proteins closely involved in bone-forming, and reducing bone resorption by mechanisms related to osteoprotegerin, RANKL and PTH receptor.

【 授权许可】

   
2013 Guerra-Menéndez et al.; licensee BioMed Central Ltd.

【 图 表 】

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