Calcium Nutrition and Extracellular Calcium Sensing: Relevance for the Pathogenesis of Osteoporosis, Cancer and Cardiovascular Diseases

Nutrients

Meinrad Peterlik¹  Enikoe Kállay² 

[1] Department of Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria;

关键词: Calcium intake;    calcium-sensing receptor;    Wnt signaling;    vitamin D;    bone formation;    colorectal cancer;    breast cancer;    hypertension;    vasculature;    cardiac functions;   

DOI  :  10.3390/nu5010302

来源: mdpi

【 摘 要 】

Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR). This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca²⁺ to function as a “first messenger” for various intracellular signaling cascades. Evidence demonstrates that Ca²⁺/CaSR signaling in functional linkage with vitamin D receptor (VDR)-activated pathways (i) promotes osteoblast differentiation and formation of mineralized bone; (ii) targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; (iii) evokes Ca²⁺ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca²⁺/CaSR signaling opens Ca²⁺-sensitive K⁺ conductance channels in vascular endothelial cells, and also participates in IP₃-dependent regulation of cytoplasmic Ca²⁺, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca²⁺/CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.