Department of Pathophysiology, University of Medicine Vienna, Vienna, Austria.
Eur J Clin Nutr. 2009 Dec;63(12):1377-86. doi: 10.1038/ejcn.2009.105. Epub 2009 Sep 2.
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-1 alpha-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 D(3) (1,25-(OH)(2)D(3)) and extracellular Ca(2+) act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)(2)D(3)-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.
维生素 D 状态受损，其特征是血清 25-羟维生素 D（25-（OH）D）水平低，以及营养性钙缺乏，在欧洲和北美国家普遍存在，与年龄或性别无关。这两种情况都与许多退行性、恶性、炎症和代谢性疾病的发病机制有关。对维生素 D 代谢酶、25-（OH）D-1α-羟化酶和 25-（OH）D-24-羟化酶的组织特异性表达和活性，以及细胞外钙敏感受体（CaR）的研究，使人们了解了非肾脏组织和细胞系统中，局部产生的 1,25-二羟维生素 D(3)（1,25-（OH）(2)D(3)）和细胞外 Ca(2+)如何作为细胞增殖、分化和功能的关键调节剂共同作用。1,25-（OH）(2)D(3)激活的维生素 D 受体（VDR）和钙缺乏时的 CaR 的协同信号转导受损，导致许多器官和生物系统的细胞功能障碍，从而增加了疾病的风险，特别是骨质疏松症、结直肠癌和乳腺癌、炎症性肠病、胰岛素依赖型糖尿病 1 型、代谢综合征、2 型糖尿病、高血压和心血管疾病。了解潜在的分子和细胞过程为提倡所有人群摄入足够的维生素 D 和钙提供了依据，从而预防了全世界许多慢性疾病。
