1. Sclerostin and DKK1: new players in renal bone and vascular disease
Pieter Evenepoel, Patrick D'Haese, Vincent Brandenburg 
Kidney International 
Volume 88, Issue 2, Pages (August 2015)
DOI: /ki
Copyright © 2015 International Society of Nephrology Terms and Conditions

2. Figure 1
The canonical Wnt–β-catenin signaling pathway and its extracellular regulation. (Left panel) Extracellular binding of Wnt to the Frz–LRP5/6 receptor complex causes intracellular accumulation of β-catenin that can induce the expression of target genes after translocation to the nucleus. (Middle panel) DKK1 dampens Wnt signaling by forming a tertiary complex with LRP5/6 and the cell surface co-receptor, Kremen-1 (KRM), thereby promoting internalization of the receptor complex. (Right panel) Sclerostin inhibits Wnt-induced signaling by binding to LRP5/6, thereby preventing Wnt to bind to the Frz–LRP5/6 receptor complex.
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

3. Figure 2
Sclerostin and the bone–vascular axis. There is intense cross-talking between the kidneys, the vasculature, and the bone. Chronic kidney disease (CKD) goes along with an increased incidence of vascular calcification and the development of adynamic bone disease. Increased renal production and circulating levels of Dickkopf-related protein 1 (DKK1) in CKD have been associated with osteochondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs), vascular calcification, and renal osteodystrophy. However, it has also been postulated that Wnt inhibitors, in particular sclerostin produced in the vascular wall, may not only have beneficial paracrine effects (retard the progression of vascular calcification) but also, when spilled over to the circulation, induce negative endocrine effects on the skeleton (decreased osteoblastogenesis and increased osteoclastogenesis). Reciprocally, the role of skeletal sclerostin in vascular pathobiology also remains to be defined. Both adynamic bone disease and vascular calcification have been associated with an increased mortality in patients with CKD.
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions