Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology
- 2 September 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in European Journal of Clinical Nutrition
- Vol. 63 (12), 1377-1386
- https://doi.org/10.1038/ejcn.2009.105
Abstract
A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1α-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and extracellular Ca2+ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)2D3-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.This publication has 94 references indexed in Scilit:
- Genetic Variation in Calcium-Sensing Receptor and Risk for Colon CancerCancer Epidemiology, Biomarkers & Prevention, 2008
- The Extracellular Calcium-Sensing Receptor (CaSR) Is a Critical Modulator of Skeletal DevelopmentScience Signaling, 2008
- Vitamin D Insufficiency: Disease or No Disease?Journal of Bone and Mineral Research, 2008
- Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary AngiographyCancer Epidemiology, Biomarkers & Prevention, 2008
- Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunityNature Clinical Practice Endocrinology & Metabolism, 2008
- Vitamin D Deficiency and Risk of Cardiovascular DiseaseCirculation, 2008
- Vitamin D signalling pathways in cancer: potential for anticancer therapeuticsNature Reviews Cancer, 2007
- The Role of Vitamin D and Calcium in Type 2 Diabetes. A Systematic Review and Meta-AnalysisJournal of Clinical Endocrinology & Metabolism, 2007
- Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanismJCI Insight, 2007
- In Vitro and In Vivo Analysis of the Immune System of Vitamin D Receptor Knockout MiceJournal of Bone and Mineral Research, 2001