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High-glucose levels and elastin degradation products accelerate osteogenesis in vascular smooth muscle cells.

ABSTRACT: Diabetes mellitus (DM) is a chronic disease in which the body either does not use or produce the glucose metabolising hormone insulin efficiently. Calcification of elastin in the arteries of diabetics is a major predictor of cardiovascular diseases. It has been previously shown that elastin degradation products work synergistically with transforming growth factor-beta 1 (TGF-?1) to induce osteogenesis in vascular smooth muscle cells. In this study, we tested the hypothesis that high concentration of glucose coupled with elastin degradation products and TGF-?1 (a cytokine commonly associated with diabetes) will cause a greater degree of osteogenesis compared to normal vascular cells. Thus, the goal of this study was to analyse the effects of high concentration of glucose, elastin peptides and TGF-?1 on bone-specific markers like alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2). We demonstrated using relative gene expression and specific protein assays that elastin degradation products in the presence of high glucose cause the increase in expression of the specific elastin-laminin receptor-1 (ELR-1) and activin receptor-like kinase-5 (ALK-5) present on the surface of the vascular cells, in turn leading to overexpression of typical osteogenic markers like ALP, OCN and RUNX2. Conversely, blocking of ELR-1 and ALK-5 strongly suppressed the expression of the osteogenic proteins. In conclusion, our results indicate that glucose plays an important role in amplifying the osteogenesis induced by elastin peptides and TGF-?1, possibly by activating the ELR-1 and ALK-5 signalling pathways.

SUBMITTER: Sinha A

PROVIDER: S-EPMC5403374 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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High-glucose levels and elastin degradation products accelerate osteogenesis in vascular smooth muscle cells.

Sinha Aditi A Vyavahare Naren R NR

Diabetes & vascular disease research 20130610 5

Diabetes mellitus (DM) is a chronic disease in which the body either does not use or produce the glucose metabolising hormone insulin efficiently. Calcification of elastin in the arteries of diabetics is a major predictor of cardiovascular diseases. It has been previously shown that elastin degradation products work synergistically with transforming growth factor-beta 1 (TGF-β1) to induce osteogenesis in vascular smooth muscle cells. In this study, we tested the hypothesis that high concentratio ...[more]

PMID: 23754846

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High-glucose levels and elastin degradation products accelerate osteogenesis in vascular smooth muscle cells.

Publications

High-glucose levels and elastin degradation products accelerate osteogenesis in vascular smooth muscle cells.

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