MEPE, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone

The MEPE (matrix extracellular phosphoglycoprotein) gene is a strong candidate for the tumor-derived phosphaturic factor in oncogenic hypophosphatemic osteomalacia,(OHO). X-linked hypophosphatemia (XLH) is phenotypically similar to OHO and results from mutations in PHEX, a putative metallopeptidase believed to process a factor(s) regulating bone mineralization and renal phosphate reabsorption. Here we report the isolation of the murine homologue of MEPE, from a bone cDNA library, that encodes a protein of 433 amino acids, 92 amino acids shorter than human MEPE. Mepe, like Phex, is expressed by fully differentiated osteoblasts and down-regulated by 1,25-(OH)(2)D-3. In contrast to Phex, Mepe expression is markedly increased during osteoblast-mediated matrix mineralization. Greater than normal Mepe mRNA levels were observed in bone and osteoblasts derived from Hyp mice, the murine homologue of human:XLH. Our data provide the first evidence that MEPE/Mepe is expressed by osteoblasts in association with mineralization. (C) 2001 Academic Press.