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Endocrinology, doi:10.1210/en.2009-0216
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Endocrinology Vol. 150, No. 9 4012-4023
Copyright © 2009 by The Endocrine Society

Matrix Extracellular Phosphoglycoprotein (MEPE) Is a New Bone Renal Hormone and Vascularization Modulator

Valentin David1, Aline Martin1, Anne-Marie Hedge and Peter S. N. Rowe

The Kidney Institute, Kansas University Medical Center, Kansas City, Kansas 66160

Address all correspondence and requests for reprints to: Peter S. N. Rowe, Department of Internal Medicine, Division of Nephrology and Hypertension, The Kidney Institute, MS 3018, 3901 Rainbow Boulevard, Kansas City, Kansas 66160. E-mail: prowe{at}kumc.edu.

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.






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Copyright © 2009 by The Endocrine Society