Do abnormal blood vessels impact bone loss in osteoporosis? (360G-Wellcome-207275_Z_17_Z)

Vascular endothelial growth factor (VEGF) has important roles in the blood vessels of adult tissues and in disease. Dr Clarkins laboratory have found that deletion of VEGF by bone forming osteoblast (osteocalcin; Ocn expressing) cells results in severe bone porosity similar to osteoporosis. To investigate how vascular endothelial cell- factors contribute to this porous phenotype, further experiments from Dr Clarkins lab collected conditioned media (CM) from osteoblasts (OBs) of mice with VEGF removed and added to vascular endothelial cells. In the absence of VEGF, endothelial cells were found to upregulate inhibitors of mineralisation including sclerostin which may contribute to osteoporotic bones of VEGF KO mice. The goal of my studentship project is to investigate how endothelial cells produce sclerostin, which is important as sclerostin has previously been reported to be secreted only by bone cells. I will investigate this by immunolabelling of sections of VEGF KO and WT long bones for sclerostin and a blood vessel marker CD31. I will also treat endothelial cells with CM from VEGF WT and KO cells and undertake Western blotting for sclerostin. Inhibiting blood vessel anti-mineralisation factors could provide a new a means to treat degenerative bone disease such as osteoporosis.