In vitro and in vivo research to investigate the role of the Wnt/beta-catenin signaling cascade in vascular calcification and the bone-vascular axis.

The calcification paradox is seen in chronic kidney disease (CKD) and osteoporosis patients and refers to the occurrence of a bone pathology characterized by a disturbed bone turnover/mineralisation in combination with calcification of the medial layer of the vessel wall; i.e. arteriosclerosis. This process of vascular calcification, which shares many similarities to bone development, is a rapidly progressive aspect of cardiovascular disease and is linked to increased morbidity and mortality particularly in CKD patients. As safe therapies to treat these mineralisation defects are urgently needed, this topic raised great interest during the last years. A pathway that might clarify the co-occurrence of mineralisation defects at the level of bone and vasculature is the Wnt/beta-catenin signalling pathway. It is known that this pathway regulates bone formation, however, its role in vascular calcification is less clear. The most obvious strategy in elucidating the potential (patho-)physiological roles of this cascade is by studying the functions of sclerostin and Dickkopf-related protein 1 (DKK1), both well-known inhibitors of the Wnt/beta-catenin signalling. Additionally, concerns are raised against the cardiovascular safety of anti-Scl and anti-DKK1 antibodies which are currently tested in clinical trials as a treatment for osteoporosis. Therefore, clarifying the mechanisms underlying this paradox is essential for the development of safe preventive and therapeutic treatments.

Keywords:KIDNEY DISEASE, OSTEOPOROSIS

Disciplines:Urology and nephrology