Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator.

Abstract:

: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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

David V,Martin A,Hedge AM,Rowe PS

doi

10.1210/en.2009-0216

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

4012-23

issue

9

eissn

0013-7227

issn

1945-7170

pii

en.2009-0216

journal_volume

150

pub_type

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