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Bone Abstracts (2014) 3 PP137 | DOI: 10.1530/boneabs.3.PP137

1MOVE research institute Amsterdam, ACTA, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands; 2MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Amsterdam, The Netherlands.

IGF1 is an osteo-anabolic factor that stimulates osteogenic precursor cell differentiation. IGF1 is produced in bone in response to mechanical stimulation, but also in mechanically-stimulated muscle cells. IGF1 enhances the rate of mRNA translation in muscle cells via activation of the PI3K/AKT/mTOR pathway, thereby increasing in muscle mass. Therefore we hypothesized that IGF1 not just enhances osteogenic differentiation of precursors, but also stimulates protein synthesis in osteoblasts, via an enhanced mRNA translation rate.

IGF1 gene expression was determined by qPCR in MC3T3-E1 osteoblasts subjected for 1 h to uni-axial cyclic strain (3 Hz, 0–5% strain). Other MC3T3-E1 osteoblasts were treated ±human recombinant IGF1 (1, 10, or 100 ng/ml) for 0.5–6 h, to determine phosphorylation of AKT (upstream of mTOR) and p70s6k (downstream of mTOR) by western blot. Osteoblasts were cultured for 1 day ± IGF1 (1, 10 or 100 ng/ml), at which time total protein and DNA were quantified, as well as mRNA expression of collagen I, transcription factors Runx2 and SP7, and IGF1 and IGF1 receptor by qPCR.

Cyclic strain of osteoblasts increased IGFI gene expression by 2.3-fold. IGF1 did not affect gene expression of collagen I, Runx2, SP7, or IGF1 receptor in osteoblasts, but IGF1 (100 ng/ml) reduced IGF1 gene expression. IGF1 enhanced AKT and p70s6k phosphorylation at 2 h and 6 h in a dose-dependent manner. IGF1 enhanced total protein by ~12-fold, while total DNA remained unchanged.

Our results confirm that mechanical stimulation enhances IGF1 expression by osteoblasts, and show that IGF1 strongly stimulates protein synthesis in osteoblasts. The anabolic effect of mechanical loading on bone may thus, at least in part, be mediated by IGF1-enhanced protein synthesis in osteoblasts. This enhanced protein synthesis is likely the result of an increased mRNA translation rate via activation of the PI3K/Akt/mTOR pathway rather than via increased mRNA transcription.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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