title: Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.
abstract: Bone morphogenetic protein-2 (BMP-2) promotes the formation and regeneration of bone and cartilage, and therefore constitutes the most promising candidate for a bone repair material. However, it also has a wide range of functions, such as in organogenesis and apoptosis. Therefore, we investigated a novel synthetic peptide corresponding to residues 73-92 of BMP-2. This peptide bound to a BMP-2-specific receptor and elevated both alkaline phosphatase activity and osteocalcin mRNA in the murine cell line, C3H10T1/2. The 73-92 peptide also induced ectopic calcification when conjugated to a covalently crosslinked alginate gel. Here we report that the 73-92 peptide-conjugated alginate gel showed prolonged ectopic calcification for up to 7 weeks in rat calf muscle. In contrast, rhBMP-2-impregnated collagen gel showed maximum ectopic calcification at 3 weeks, and the calcified products that had formed disappeared after 5 weeks. Histological examination showed that the 73-92 peptide-conjugated alginate gel induced many osteoblast-like cells and few osteoclasts. In contrast, rhBMP-2-impregnated collagen gel induced many osteoclasts. These results suggest that the 73-92 peptide on alginate gel remains active at the implanted site, continuously induces differentiation of osteoblast precursor cells into osteoblasts, and activates osteoblasts to promote ectopic calcification.
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ogata
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohtsuki
authors.forename: Masao
authors.initials: M
authors.lastname: Tanihara
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D005782:Gels; D007700:Kinetics; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D018482:Muscle, Skeletal / Q000473:pathology; D009999:Ossification, Heterotopic / Q000139:chemically induced*; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D000464:Alginates; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003432:Cross-Linking Reagents; D005782:Gels; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta