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In vivo evidence of IGF-I-estrogen crosstalk in mediating the cortical bone response to mechanical strain.

Mohan S, Bhat CG, Wergedal JE, Kesavan C - Bone Res (2014)

Bottom Line: Two weeks of mechanical loading caused a 7%-8% and an 11%-13% (P<0.05 vs. non-loaded bones) increase in cortical BMD and cortical thickness (Ct.Th), respectively, in the control sham, control pOVX and H IGF-I KO sham groups.The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant (P<0.05) by two-way ANOVA.In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Disease Center, VA Loma Linda Healthcare System , Loma Linda, CA, USA ; Department of Medicine, Loma Linda University , Loma Linda, CA, USA ; Department of Biochemistry, Loma Linda University , Loma Linda, CA, USA ; Department of Physiology, Loma Linda University , Loma Linda, CA, USA.

ABSTRACT
Although insulin-like growth factor-I (IGF-I) and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading. To test this, at 5 weeks of age, partial ovariectomy (pOVX) or a sham operation was performed on heterozygous IGF-I conditional knockout (H IGF-I KO) and control mice generated using a Cre-loxP approach. At 10 weeks of age, a 10 N axial load was applied on the right tibia of these mice for a period of 2 weeks and the left tibia was used as an internal non-non-loaded control. At the cortical site, partial estrogen loss reduced total volumetric bone mineral density (BMD) by 5% in control pOVX mice (P=0.05, one-way ANOVA), but not in the H IGF-I KO pOVX mice. At the trabecular site, bone volume/total volume (BV/TV) was reduced by 5%-6% in both control pOVX (P<0.05) and H IGF-I KO pOVX (P=0.05) mice. Two weeks of mechanical loading caused a 7%-8% and an 11%-13% (P<0.05 vs. non-loaded bones) increase in cortical BMD and cortical thickness (Ct.Th), respectively, in the control sham, control pOVX and H IGF-I KO sham groups. By contrast, the magnitude of cortical BMD (4%, P=0.13) and Ct.Th (6%, P<0.05) responses were reduced by 50% in the H IGF-I KO pOVX mice compared to the other three groups. The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant (P<0.05) by two-way ANOVA. Two weeks of axial loading caused similar increases in trabecular BV/TV (13%-17%) and thickness (17%-23%) in all four groups of mice. In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.

No MeSH data available.


Related in: MedlinePlus

Micro-CT measurement of tibia cortical bone parameters (a) TV, (b) BMD and (c) Ct.Th in H IGF-I KO and control mice with sham or pOVX groups after 2 weeks of axial loading. Values are the mean±s.e., N=5/group, AP<0.05 vs. control sham and control pOVX, BP<0.05 vs. non-loaded tibias, P=0.08 vs. control sham mice, CP<0.05 vs. H IGF-I KO sham and H IGF-I KO pOVX and DP=0.08 vs. H IGF-I KO pOVX mice.
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fig2: Micro-CT measurement of tibia cortical bone parameters (a) TV, (b) BMD and (c) Ct.Th in H IGF-I KO and control mice with sham or pOVX groups after 2 weeks of axial loading. Values are the mean±s.e., N=5/group, AP<0.05 vs. control sham and control pOVX, BP<0.05 vs. non-loaded tibias, P=0.08 vs. control sham mice, CP<0.05 vs. H IGF-I KO sham and H IGF-I KO pOVX and DP=0.08 vs. H IGF-I KO pOVX mice.

Mentions: pOVX did not affect cross sectional area at the mid diaphysis region either in the control mice or in H IGF-I KO mice when compared to corresponding sham groups (Figure 2a). However, total BMD was decreased by 5% in control pOVX mice when compared to control sham mice (P=0.08) (Figure 2b). This decrease in BMD in the control pOVX mice, however, did not achieve statistical significance (P=0.16) by two-way ANOVA. The H IGF-I KO mice with pOVX did not show a decrease in BMD when compared to H IGF-I KO sham mice (Figure 2b). Two-way ANOVA analysis revealed no significant difference in the cortical thickness between the pOVX and sham groups (Figure 2c).


In vivo evidence of IGF-I-estrogen crosstalk in mediating the cortical bone response to mechanical strain.

Mohan S, Bhat CG, Wergedal JE, Kesavan C - Bone Res (2014)

Micro-CT measurement of tibia cortical bone parameters (a) TV, (b) BMD and (c) Ct.Th in H IGF-I KO and control mice with sham or pOVX groups after 2 weeks of axial loading. Values are the mean±s.e., N=5/group, AP<0.05 vs. control sham and control pOVX, BP<0.05 vs. non-loaded tibias, P=0.08 vs. control sham mice, CP<0.05 vs. H IGF-I KO sham and H IGF-I KO pOVX and DP=0.08 vs. H IGF-I KO pOVX mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472140&req=5

fig2: Micro-CT measurement of tibia cortical bone parameters (a) TV, (b) BMD and (c) Ct.Th in H IGF-I KO and control mice with sham or pOVX groups after 2 weeks of axial loading. Values are the mean±s.e., N=5/group, AP<0.05 vs. control sham and control pOVX, BP<0.05 vs. non-loaded tibias, P=0.08 vs. control sham mice, CP<0.05 vs. H IGF-I KO sham and H IGF-I KO pOVX and DP=0.08 vs. H IGF-I KO pOVX mice.
Mentions: pOVX did not affect cross sectional area at the mid diaphysis region either in the control mice or in H IGF-I KO mice when compared to corresponding sham groups (Figure 2a). However, total BMD was decreased by 5% in control pOVX mice when compared to control sham mice (P=0.08) (Figure 2b). This decrease in BMD in the control pOVX mice, however, did not achieve statistical significance (P=0.16) by two-way ANOVA. The H IGF-I KO mice with pOVX did not show a decrease in BMD when compared to H IGF-I KO sham mice (Figure 2b). Two-way ANOVA analysis revealed no significant difference in the cortical thickness between the pOVX and sham groups (Figure 2c).

Bottom Line: Two weeks of mechanical loading caused a 7%-8% and an 11%-13% (P<0.05 vs. non-loaded bones) increase in cortical BMD and cortical thickness (Ct.Th), respectively, in the control sham, control pOVX and H IGF-I KO sham groups.The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant (P<0.05) by two-way ANOVA.In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.

View Article: PubMed Central - PubMed

Affiliation: Musculoskeletal Disease Center, VA Loma Linda Healthcare System , Loma Linda, CA, USA ; Department of Medicine, Loma Linda University , Loma Linda, CA, USA ; Department of Biochemistry, Loma Linda University , Loma Linda, CA, USA ; Department of Physiology, Loma Linda University , Loma Linda, CA, USA.

ABSTRACT
Although insulin-like growth factor-I (IGF-I) and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading. To test this, at 5 weeks of age, partial ovariectomy (pOVX) or a sham operation was performed on heterozygous IGF-I conditional knockout (H IGF-I KO) and control mice generated using a Cre-loxP approach. At 10 weeks of age, a 10 N axial load was applied on the right tibia of these mice for a period of 2 weeks and the left tibia was used as an internal non-non-loaded control. At the cortical site, partial estrogen loss reduced total volumetric bone mineral density (BMD) by 5% in control pOVX mice (P=0.05, one-way ANOVA), but not in the H IGF-I KO pOVX mice. At the trabecular site, bone volume/total volume (BV/TV) was reduced by 5%-6% in both control pOVX (P<0.05) and H IGF-I KO pOVX (P=0.05) mice. Two weeks of mechanical loading caused a 7%-8% and an 11%-13% (P<0.05 vs. non-loaded bones) increase in cortical BMD and cortical thickness (Ct.Th), respectively, in the control sham, control pOVX and H IGF-I KO sham groups. By contrast, the magnitude of cortical BMD (4%, P=0.13) and Ct.Th (6%, P<0.05) responses were reduced by 50% in the H IGF-I KO pOVX mice compared to the other three groups. The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant (P<0.05) by two-way ANOVA. Two weeks of axial loading caused similar increases in trabecular BV/TV (13%-17%) and thickness (17%-23%) in all four groups of mice. In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.

No MeSH data available.


Related in: MedlinePlus