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MEPE  -  matrix extracellular phosphoglycoprotein

Homo sapiens

Synonyms: Matrix extracellular phosphoglycoprotein, OF45, Osteoblast/osteocyte factor 45
 
 
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Disease relevance of MEPE

  • MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia [1].
  • MEPE (Matrix Extracellular PhosphoglycoprotEin) expression is markedly elevated in X-linked-hypophosphatemic-rickets (HYP) and tumor-induced osteomalacia (TIO) [2].
  • In the pre-treatment, only a higher dose (200nM) of MPEP significantly prevented the magnitude of weight load reduction, whereas AIDA (200muM) and MEPE (50, 100 and 200nM) significantly reduced the development of mechanical hyperalgesia compared to saline treated group [3].
  • In group S (single injection, n = 53) 80 mL MEPE 1% were injected into the neurovascular sheath, transarterially or after eliciting paresthesia [4].
 

Psychiatry related information on MEPE

  • The average doses of MEPE were 3.5 mg x kg(-1) (2.4-5.6) in T group and 12.0 mg x kg(-1) (8.9-16.4), in S group [4].
 

High impact information on MEPE

 

Biological context of MEPE

  • FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization [7].
  • Refined mapping localizes MEPE to 4q21.1 between ESTs D4S2785 (WI-6336) and D4S2844 (WI-3770) [1].
  • 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 [8].
  • The resulting coordination of mineralization and release of a phosphaturic factor by MEPE may serve a physiological role in regulating systemic phosphate homeostasis to meet the needs for bone mineralization [9].
  • Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity [9].
 

Anatomical context of MEPE

 

Associations of MEPE with chemical compounds

  • All the proteins including MEPE contain RGD sequence motifs that are proposed to be essential for integrin-receptor interactions [1].
  • Analysis of human brain mRNA by RT-PCR has led to the discovery of two additional exons thereby making it more convincing that MEPE is a member of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family [13].
  • The spreading of the PAC at the air/water interface results in a Langmuir film with a stratified architecture, such that DHP forms a monolayer on the water surface, while the metallosupramolecular coordination polyelectrolyte (MEPE) is immersed in the aqueous subphase [14].
  • However, when cultured in the presence of 5 mM beta-glycerophosphate, ascorbate, and dexamethasone for 29 days, which are similar conditions to those described by Owen in his differentiation model in rat osteoblasts, a progressive inhibition of MEPE gene expression to 20% of the maximum was observed [15].
  • In group T (targeted injections, n = 53) the four terminal nerves were located by electrical stimulation, and anesthetized with 5 ml mepivacaine 1% with epinephrine 5 microg x ml(-1) (MEPE) [4].
 

Physical interactions of MEPE

  • Our aims were to determine (1) whether PHEX binds specifically to MEPE, (2) whether the binding involves the ASARM motif region, and (3) whether free ASARM peptide affects mineralization in vivo in mice [16].
 

Enzymatic interactions of MEPE

  • We found that both recombinant MEPE and synthetic phosphorylated ASARM peptide (ASARM-PO(4)) inhibit PHEX enzyme activities in an in vitro fluorescent-quenched PHEX enzyme activity assay [9].
 

Regulatory relationships of MEPE

  • These findings suggest that MEPE inhibits mineralization and PHEX activity and leads to increased FGF23 production [9].
 

Other interactions of MEPE

 

Analytical, diagnostic and therapeutic context of MEPE

  • Three of 11 non-OHO tumors screened contained trace levels of MEPE expression (detected only after RT-PCR and Southern 32P analysis) [1].
  • Protein interactions between MEPE and recombinant soluble PHEX (secPHEX) were measured using surface plasmon resonance (SPR) [16].
  • In order to begin to address the role of MEPE in normal human physiology, we developed a competitive ELISA to measure serum levels of MEPE [20].
  • Using this antibody, we analyzed the distribution of MEPE in human bones by immunohistochemistry [21].
  • CONCLUSIONS: Small targeted injections of MEPE reduce total anesthetic time, give better spread of analgesia in the hand and forearm, and may be safer than a single large injection [4].

References

  1. MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Rowe, P.S., de Zoysa, P.A., Dong, R., Wang, H.R., White, K.E., Econs, M.J., Oudet, C.L. Genomics (2000) [Pubmed]
  2. Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets. Bresler, D., Bruder, J., Mohnike, K., Fraser, W.D., Rowe, P.S. J. Endocrinol. (2004) [Pubmed]
  3. The peripheral role of group I metabotropic glutamate receptors on nociceptive behaviors in rats with knee joint inflammation. Lee, K.S., Kim, J., Yoon, Y.W., Lee, M.G., Hong, S.K., Han, H.C. Neurosci. Lett. (2007) [Pubmed]
  4. Low dose axillary block by targeted injections of the terminal nerves. Koscielniak-Nielsen, Z.J., Rotbøll Nielsen, P., Sørensen, T., Stenør, M. Canadian journal of anaesthesia = Journal canadien d'anesthésie. (1999) [Pubmed]
  5. Coexpression of CCR5 and IL-2 in human genital but not blood T cells: implications for the ontogeny of the CCR5+ Th1 phenotype. Hladik, F., Lentz, G., Delpit, E., McElroy, A., McElrath, M.J. J. Immunol. (1999) [Pubmed]
  6. A synthetic peptide fragment of human MEPE stimulates new bone formation in vitro and in vivo. Hayashibara, T., Hiraga, T., Yi, B., Nomizu, M., Kumagai, Y., Nishimura, R., Yoneda, T. J. Bone Miner. Res. (2004) [Pubmed]
  7. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Quarles, L.D. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  8. Mepe, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone. Argiro, L., Desbarats, M., Glorieux, F.H., Ecarot, B. Genomics (2001) [Pubmed]
  9. Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity. Liu, S., Rowe, P.S., Vierthaler, L., Zhou, J., Quarles, L.D. J. Endocrinol. (2007) [Pubmed]
  10. Renal expression of SIBLING proteins and their partner matrix metalloproteinases (MMPs). Ogbureke, K.U., Fisher, L.W. Kidney Int. (2005) [Pubmed]
  11. Expression of SIBLINGs and their partner MMPs in salivary glands. Ogbureke, K.U., Fisher, L.W. J. Dent. Res. (2004) [Pubmed]
  12. MEPE/OF45, a new dentin/bone matrix protein and candidate gene for dentin diseases mapping to chromosome 4q21. MacDougall, M., Simmons, D., Gu, T.T., Dong, J. Connect. Tissue Res. (2002) [Pubmed]
  13. Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Fisher, L.W., Fedarko, N.S. Connect. Tissue Res. (2003) [Pubmed]
  14. Structural analysis of a metallosupramolecular polyelectrolyte-amphiphile complex at the air/water interface. Lehmann, P., Kurth, D.G., Brezesinski, G., Symietz, C. Chemistry (Weinheim an der Bergstrasse, Germany) (2001) [Pubmed]
  15. Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts. Siggelkow, H., Schmidt, E., Hennies, B., Hüfner, M. Bone (2004) [Pubmed]
  16. Surface plasmon resonance (SPR) confirms that MEPE binds to PHEX via the MEPE-ASARM motif: a model for impaired mineralization in X-linked rickets (HYP). Rowe, P.S., Garrett, I.R., Schwarz, P.M., Carnes, D.L., Lafer, E.M., Mundy, G.R., Gutierrez, G.E. Bone (2005) [Pubmed]
  17. Phosphate diabetes, tubular phosphate reabsorption and phosphatonins. Laroche, M., Boyer, J.F. Joint, bone, spine : revue du rhumatisme. (2005) [Pubmed]
  18. A fragment of the hypophosphatemic factor, MEPE, requires inducible cyclooxygenase-2 to exert potent anabolic effects on normal human marrow osteoblast precursors. Nagel, D.E., Khosla, S., Sanyal, A., Rosen, D.M., Kumagai, Y., Riggs, B.L. J. Cell. Biochem. (2004) [Pubmed]
  19. MEPE is downregulated as dental pulp stem cells differentiate. Liu, H., Li, W., Shi, S., Habelitz, S., Gao, C., Denbesten, P. Arch. Oral Biol. (2005) [Pubmed]
  20. Serum levels of matrix extracellular phosphoglycoprotein (MEPE) in normal humans correlate with serum phosphorus, parathyroid hormone and bone mineral density. Jain, A., Fedarko, N.S., Collins, M.T., Gelman, R., Ankrom, M.A., Tayback, M., Fisher, L.W. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  21. Matrix extracellular phosphoglycoprotein (MEPE) is highly expressed in osteocytes in human bone. Nampei, A., Hashimoto, J., Hayashida, K., Tsuboi, H., Shi, K., Tsuji, I., Miyashita, H., Yamada, T., Matsukawa, N., Matsumoto, M., Morimoto, S., Ogihara, T., Ochi, T., Yoshikawa, H. J. Bone Miner. Metab. (2004) [Pubmed]
 
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