title: Sclerostin and CKD-MBD.
abstract: Declining kidney function is associated with sequential systemic changes in mineral homeostasis leading to pathologic alterations in the cardiovascular system and the skeleton. One of the earliest changes in response to renal injury is the increased osteocyte production of secreted factors including the anti-anabolic protein, sclerostin. Elevated sclerostin is associated with reduced Wnt/β-catenin signaling in bone and decreased osteoblast differentiation/activity. Agents that directly or indirectly inhibit β-catenin signaling have differential skeletal effects suggesting additional mechanisms contribute to the diversity of renal osteodystrophies. Similarly, Wnt/β-catenin activation in smooth muscle cells contributes to cardiovascular calcification yet emerging data suggests that this pathway may also be protective when elevated in neighboring tissues. The ongoing epidemiology studies examining the relationship between circulating sclerostin and cardiovascular disease, particularly those that investigate stage specific and/or patient sub-populations, will be useful in understanding the overall contributions of this pathway, its antagonist sclerostin, and the progression of CKD-MBD.
authors.affiliation: Genzyme, Boston, MA, USA, scschiavi@gmail.com.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Schiavi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D018450:Disease Progression; D005819:Genetic Markers / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013577:Syndrome; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D051153:Wnt Proteins; D051176:beta Catenin