1. IGF-I increases markers of osteoblastic activity and reduces bone resorption via osteoprotegerin and RANK-ligand.
- Author
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Guerra-Menéndez, Lucia, Sádaba, Maria C., Puche, Juan E., Lavandera, Jose L., de Castro, Luis F., de Gortázar, Arancha R., and Castilla-Cortázar, Inma
- Subjects
SOMATOMEDIN C ,BONE resorption ,OSTEOPROTEGERIN ,TRANCE protein ,OSTEOPENIA - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2013
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