The role of sclerostin in vascular calcification and the calcification paradox: necessary research for development of safe therapies to treat mineralization defects in bone and vessels.

Cardiovascular disease is responsible for a substantial part of mortality in patients with chronic kidney disease (CKD) or diabetes (also a cause of CKD). Vascular calcification (VC) is a rapidly progressive, prominent aspect of cardiovascular disease in these patients as well as in those with osteoporosis. Remarkably, pathological VC in these patient groups goes along with disturbed bone metabolism. This association is called the calcification paradox. Development of new, safe therapies to treat the mineralization defects in bone and vessels is urgently needed. Sclerostin (Scl) is a protein produced by bone cells (osteocytes), inhibiting bone formation and mineralization. VC is regulated similarly to that of developing bone: vascular smooth muscle cells (VSMC) transdifferentiate to cells with a bone-like phenotype and proteins involved in bone formation also regulate the development of VC. Scl expression has been found in VSMC during calcification and CKD patients with VC were observed to have higher serum Scl. The Laboratory of Pathophysiology was the first to find an association between increased serum Scl and decreased mortality in hemodialysis patients. Hence, it is not surprising that during the last years the potential role of Scl in vascular pathophysiology and the calcification paradox has received increasing interest. This project aims to elucidate the complex role of Scl in mineralistation defects of bone and vessels and their reciprocal effects onto each other -

Keywords:SCLEROSTIN

Disciplines:Cardiac and vascular medicine

Project type:Collaboration project