MEPE's diverse effects on mineralization.
Matrix extracellular phosphoglycoprotein (MEPE) is an inhibitor of mineralization in situ and in cell cultures where altered expression is associated with oncogenic osteomalacia and hypophosphatemic rickets. The purpose of this study was to determine whether the intact protein or the peptide(s) originating from this protein was responsible for the inhibition. The ability of the intact protein and the acidic, serine- and aspartate-rich MEPE-associated motif (ASARM) peptide to promote or inhibit de novo hydroxyapatite formation and growth of hydroxyapatite seed crystals, in both phosphorylated and dephosphorylated forms, was assessed at room temperature in a dynamic gel diffusion system at 3.5 and 5 days. The most effective nucleator concentration was also examined when associated with fibrillar type I collagen. The phosphorylated intact protein was an effective promoter of mineralization in the gelatin gel diffusion system, while the ASARM peptide was an effective inhibitor. When dephosphorylated both the intact protein and the ASARM peptide had no effect on mineralization. Associated with collagen fibrils, some of the effect of the intact protein was lost. This study demonstrates the importance of posttranslational modification for the site-specific activity of MEPE and its ASARM peptide.
Boskey
Adele L
AL
Musculoskeletal Integrity Program, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. Boskeya@hss.edu
Chiang
Phyllis
P
Fermanis
Alexis
A
Brown
Jared
J
Taleb
Hayat
H
David
Valentin
V
Rowe
Peter S N
PS
D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002113:Calcification, Physiologic / Q000502:physiology*; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D017886:Durapatite / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005782:Gels / Q000737:chemistry; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010018:Osteomalacia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D046188:Protein Modification, Translational / Q000187:drug effects / Q000502:physiology
D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005782:Gels; D006023:Glycoproteins; C486579:MEPE protein, human; D010446:Peptide Fragments; D010750:Phosphoproteins; D017886:Durapatite