Department of Dermatology and Cutaneous Biology, Jefferson Medical College and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Exp Dermatol. 2012 Sep;21(9):694-9. doi: 10.1111/j.1600-0625.2012.01553.x.
Ectopic mineralization, linked to a number of diseases, is a major cause of morbidity and mortality in humans. Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by calcium phosphate deposition in various tissues. The mineral content of diet has been suggested to modify the disease severity in PXE. The aim of this study is to explore the role of diet with reduced magnesium in modifying tissue mineralization in a mouse model of PXE. Abcc6(-/-) mice were placed on either standard rodent diet (control) or an experimental diet low in magnesium at weaning (4 weeks) and examined for mineralization in the skin and internal organs at the ages of 1.5, 2 or 6 months by computerized morphometric analysis of histopathological sections and by chemical assay of calcium and phosphate. Abcc6(-/-) mice on experimental diet demonstrated an accelerated, early-onset mineralization of connective tissues, as compared to control mice. Wild-type or heterozygous mice on experimental diet did not show evidence of mineralization up to 6 months of age. All mice on experimental diet showed decreased urinary calcium, increased urinary phosphate and elevated parathyroid serum levels. However, no difference in bone density at 6 months of age was noted. Our findings indicate that the mineral content, particularly magnesium, can modify the extent and the onset of mineralization in Abcc6(-/-) mice and suggest that dietary magnesium levels may contribute to the phenotypic variability of PXE. The control of mineralization by dietary magnesium may have broader implications in general population in the context of vascular mineralization.
异位矿化与许多疾病有关，是导致人类发病率和死亡率的主要原因。弹性假黄瘤（PXE）是一种遗传性多系统疾病，其特征是在各种组织中沉积磷酸钙。饮食中的矿物质含量被认为可以改变 PXE 的疾病严重程度。本研究旨在探索低镁饮食在改变 PXE 小鼠模型中组织矿化方面的作用。从断奶（4 周）开始，将 Abcc6（-/-）小鼠置于标准啮齿动物饮食（对照）或低镁实验饮食中，并在 1.5、2 或 6 月龄时通过计算机形态计量分析组织病理学切片和化学分析钙和磷酸盐来检查皮肤和内脏器官中的矿化情况。与对照小鼠相比，低镁饮食组的 Abcc6（-/-）小鼠表现出结缔组织矿化的加速、早发。在 6 个月龄时，实验饮食的野生型或杂合型小鼠均未出现矿化迹象。所有低镁饮食的小鼠的尿钙减少，尿磷增加，甲状旁腺血清水平升高。然而，在 6 个月龄时，骨密度没有差异。我们的发现表明，矿物质含量，特别是镁，可以改变 Abcc6（-/-）小鼠中矿化的程度和发生时间，并表明饮食中镁水平可能导致 PXE 的表型变异性。饮食镁对矿化的控制可能在血管矿化的背景下对一般人群具有更广泛的意义。
