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Peptides from Phage Display Library Modulate Gene Expression in Mesenchymal Cells and Potentiate Osteogenesis in Unicortical Bone Defects
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Peptides from Phage Display Library Modulate Gene Expression in Mesenchymal Cells and Potentiate Osteogenesis in Unicortical Bone Defects

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

L Argiro1, M Desbarats, F H Glorieux

  • 1Genetics Unit, Shriners Hospital, Montreal, Quebec, H3G 1A6, Canada.

Genomics
|June 21, 2001
PubMed

Insights

Matrix extracellular phosphoglycoprotein (MEPE) is linked to oncogenic hypophosphatemic osteomalacia. This study identifies the murine MEPE homolog and shows its increased expression during bone mineralization in X-linked hypophosphatemia models.

Area of Science:

  • Biochemistry
  • Genetics
  • Molecular Biology

Background:

  • The matrix extracellular phosphoglycoprotein (MEPE) gene is a candidate for the phosphaturic factor in oncogenic hypophosphatemic osteomalacia (OHO).
  • X-linked hypophosphatemia (XLH) shares similarities with OHO and involves mutations in PHEX, a metallopeptidase regulating phosphate homeostasis.
  • PHEX is believed to process factors affecting bone mineralization and renal phosphate reabsorption.

Purpose of the Study:

  • To isolate and characterize the murine homolog of the MEPE gene.
  • To investigate the expression pattern of Mepe in osteoblasts and its association with mineralization.
  • To examine Mepe expression in the murine model of XLH (Hyp mice).

Main Methods:

  • Isolation of the murine MEPE homolog from a bone cDNA library.
  • Analysis of Mepe protein and mRNA expression in osteoblasts.
  • Comparison of Mepe expression in normal and Hyp mice.

Main Results:

  • The murine MEPE homolog encodes a 433-amino acid protein, 92 amino acids shorter than human MEPE.
  • Mepe is expressed by differentiated osteoblasts and down-regulated by 1,25-(OH)2D3.
  • Mepe expression increases during osteoblast-mediated matrix mineralization, and elevated mRNA levels are found in Hyp mice.

Conclusions:

  • MEPE/Mepe is expressed by osteoblasts in association with mineralization.
  • This finding provides a link between MEPE and the pathophysiology of hypophosphatemic disorders.
  • Further research into MEPE's role could elucidate mechanisms of phosphate regulation and bone mineralization.

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