Matrix Extracellular Phosphoglycoprotein (MEPE) Is a New Bone Renal Hormone and Vascularization Modulator
Matrix Extracellular Phosphoglycoprotein (MEPE) Is a New Bone Renal Hormone and Vascularization Modulator
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DOI：
10.1210/en.2009-0216
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发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
Rowe, Peter S. N.
中科院分区：
文献类型：
--
作者：
David, Valentin;Martin, Aline;Rowe, Peter S. N.
基质细胞外磷酸糖蛋白（MEPE）表达增加发生在几种磷酸盐和骨矿物质代谢紊乱。为了解决MEPE是否起作用，我们建立了在骨中过表达MEPE蛋白（MEPE tgn）的小鼠模型。MEPE tgn小鼠表现出生长和矿化缺陷，骨-肾血管化改变，持续到成年。生长矿化缺陷是由于骨重建减少，MEPE tgn小鼠对饮食诱导的肾钙化有抵抗力。MEPE蛋白衍生的尿ASARM肽和减少的尿Ca X PO 4产物介导了抑制的肾钙化。成骨细胞活性降低，但分化正常。成骨细胞存在时，骨细胞前体不能分化。在肾脏中，NPT 2a上调诱导磷酸盐肾重吸收增加，导致高磷血症。我们得出结论，MEPE和MEPE-磷酸调节基因与X染色体上的内肽酶（MEPE-PHEX）相互作用的同源性是年龄-饮食依赖性途径的组成部分，调节骨转换和矿化，抑制肾钙化。这种新的途径还调节骨-肾血管化和骨转换。（内分泌学150：4012-4023，2009）
Increased matrix extracellular phosphoglycoprotein (MEPE) expression occurs in several phosphate and bone-mineral metabolic disorders. To resolve whether MEPE plays a role, we created a murine model overexpressing MEPE protein (MEPE tgn) in bone. MEPE tgn mice displayed a growth and mineralization defect with altered bone-renal vascularization that persisted to adulthood. The growth mineralization defect was due to a decrease in bone remodeling, and MEPE tgn mice were resistant to diet-induced renal calcification. MEPE protein-derived urinary ASARM peptides and reduced urinary Ca X PO4 product mediated the suppressed renal calcification. Osteoblastic cells displayed reduced activity but normal differentiation. Osteoclastic precursors were unable to differentiate in the presence of osteoblasts. In the kidney, NPT2a up-regulation induced an increase in phosphate renal reabsorption, leading to hyperphosphatemia. We conclude MEPE and MEPE-phosphate-regulating gene with homologies to endopeptidases on the X chromosome (MEPE-PHEX) interactions are components to an age-diet-dependent pathway that regulates bone turnover and mineralization and suppresses renal calcification. This novel pathway also modulates bone-renal vascularization and bone turnover. (Endocrinology 150: 4012-4023, 2009)