Article Abstract

Sclerostin, bone morphogenetic protein, Wnt and the lung: a potential role beyond bone metabolism?

Authors: Valentina Biasin, Barbara Obermayer-Pietsch

Abstract

Sclerostin is a secreted glycoprotein encoded by the SOST gene. Mutation to SOST are responsible for sclerosis of the skeleton leading to Van Buchen disease and sclerosteosis. Sclerostin has been hence described as a negative regulator of bone mineralization. Molecular studies revealed that sclerostin decreased osteoblasts differentiation and activity via inhibition of the bone morphogenetic protein (BMP)-induced canonical Wnt pathway. Recently, sclerostin has been described to be expressed not exclusively in the bone but in other tissue and organs such as smooth muscle cells of the vasculature and lung. Attenuation and de-regulation of BMP and Wnt pathways are very well described in pulmonary hypertension (PH), a condition where increased pulmonary vascular resistance leads to remodelling of the vascular wall with narrowing or occlusion of the vessel lumen and ultimately right heart failure. Here we suggest a potential role of sclerostin in altering homeostasis of endothelial and smooth muscle cells of the pulmonary vessel wall, thereby contributing to the development and progression of PH.