Effect of diabete mellitus on osteoblastic differentiation of mesenchymal stem cells

Abstract

Diabetes mellitus (DM) is characterized by high glucose concentrations in blood that is caused by decreased or fail in insulin secretion. The most common DM are classified as type 1 and 2 and both have negative effect on bone tissue, at least in part, by impairing the osteoblastic differentiation and decreasing osteoblatic functions. High glucose concentration can inhibit the proliferation of osteoprogenitors and osteoblasts decreasing the gene expression of bone markers and the mineralization of extracellular matrix. However, there is not studies comparing the distinct effects of DM1 and DM2 on osteoblastic differentiation or evaluating which cellular signaling pathways are involved in these effects. So, the aims of this study are to evaluated the effects of DM1 and DM2 on the osteoblastic differentiation of mesenchymal stem cells and the participation of the BMP, Wnt and integrins cell signaling pathways in this process. For this, either DM1 or DM2 will be induced in Wistar rats from which mesenchymal stem cells will be harvested from bone marrow and cultured to be differentiated into osteoblasts under hyperglicemic conditions. Cells will be evaluated for proliferation, alkaline phosphatase activity, gene expression of the bone markers Runx2, OSX, ALP, BSP and OC. By using an array the expression of genes involved in the signaling pathways of BMP, Wnt and integrins will be also evaluated. (AU)