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

Guerra-Menéndez L, Sádaba MC, Puche JE, Lavandera JL, de Castro LF, de Gortázar AR, Castilla-Cortázar I - J Transl Med (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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.

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Related in: MedlinePlus

Serum IGF-I levels and their correlations with IGFBP-3 and body weight. A. Serum levels of IGF-I in controls (CO) mice with partial IGF-I deficiency (Hz) and Hz treated with low dose of IGF-I for 10 days. B. Direct and significant correlations between IGF-I and IGFBP-3. Data obtained from animals from the three experimental groups (n = 8 each group). C. Correlation between IGF-I and body weight. Data obtained from animals from the three experimental groups (n = 8 each group). **p < 0.01 CO vs Hz. &&p < 0.01 Hz vs Hz + IGF-I.
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Figure 1: Serum IGF-I levels and their correlations with IGFBP-3 and body weight. A. Serum levels of IGF-I in controls (CO) mice with partial IGF-I deficiency (Hz) and Hz treated with low dose of IGF-I for 10 days. B. Direct and significant correlations between IGF-I and IGFBP-3. Data obtained from animals from the three experimental groups (n = 8 each group). C. Correlation between IGF-I and body weight. Data obtained from animals from the three experimental groups (n = 8 each group). **p < 0.01 CO vs Hz. &&p < 0.01 Hz vs Hz + IGF-I.

Mentions: Accordingly to previous data [21], heterozygous (Hz) animals showed significantly lower levels of serum IGF-I serum as compared to control group (Hz: 372.65 ± 23.52 vs CO: 891.93 ± 60.51 ng/mL, p < 0.01). Interestingly, low doses of IGF-I were able to restore normal circulating levels of IGF-I (Hz + IGF-I: 869.42 ± 101.22 ng/mL, p < 0.01), p = n.s. vs CO, p < 0.01 vs Hz), acting as a real replacement therapy (Figure 1A).


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

Guerra-Menéndez L, Sádaba MC, Puche JE, Lavandera JL, de Castro LF, de Gortázar AR, Castilla-Cortázar I - J Transl Med (2013)

Serum IGF-I levels and their correlations with IGFBP-3 and body weight. A. Serum levels of IGF-I in controls (CO) mice with partial IGF-I deficiency (Hz) and Hz treated with low dose of IGF-I for 10 days. B. Direct and significant correlations between IGF-I and IGFBP-3. Data obtained from animals from the three experimental groups (n = 8 each group). C. Correlation between IGF-I and body weight. Data obtained from animals from the three experimental groups (n = 8 each group). **p < 0.01 CO vs Hz. &&p < 0.01 Hz vs Hz + IGF-I.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231608&req=5

Figure 1: Serum IGF-I levels and their correlations with IGFBP-3 and body weight. A. Serum levels of IGF-I in controls (CO) mice with partial IGF-I deficiency (Hz) and Hz treated with low dose of IGF-I for 10 days. B. Direct and significant correlations between IGF-I and IGFBP-3. Data obtained from animals from the three experimental groups (n = 8 each group). C. Correlation between IGF-I and body weight. Data obtained from animals from the three experimental groups (n = 8 each group). **p < 0.01 CO vs Hz. &&p < 0.01 Hz vs Hz + IGF-I.
Mentions: Accordingly to previous data [21], heterozygous (Hz) animals showed significantly lower levels of serum IGF-I serum as compared to control group (Hz: 372.65 ± 23.52 vs CO: 891.93 ± 60.51 ng/mL, p < 0.01). Interestingly, low doses of IGF-I were able to restore normal circulating levels of IGF-I (Hz + IGF-I: 869.42 ± 101.22 ng/mL, p < 0.01), p = n.s. vs CO, p < 0.01 vs Hz), acting as a real replacement therapy (Figure 1A).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus