title: IGF-I increases markers of osteoblastic activity and reduces bone resorption via osteoprotegerin and RANK-ligand.
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.
authors.forename: Lucia
authors.initials: L
authors.lastname: Guerra-Menéndez
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sádaba
authors.forename: Juan E
authors.initials: JE
authors.lastname: Puche
authors.forename: Jose L
authors.initials: JL
authors.lastname: Lavandera
authors.forename: Luis F
authors.initials: LF
authors.lastname: de Castro
authors.forename: Arancha R
authors.initials: AR
authors.lastname: de Gortázar
authors.affiliation: 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. iccortazar@ceu.es.
authors.forename: Inma
authors.initials: I
authors.lastname: Castilla-Cortázar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001862:Bone Resorption; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; D007334:Insulin-Like Growth Factor I