1. Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope.
- Author
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Saito A, Suzuki Y, Ogata Si, Ohtsuki C, and Tanihara M
- Subjects
- Alginates metabolism, Alkaline Phosphatase metabolism, Amino Acid Sequence, Animals, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins chemistry, Bone Morphogenetic Proteins genetics, Bone and Bones cytology, Calcification, Physiologic physiology, Cell Line, Gels metabolism, Humans, Male, Mice, Muscle, Skeletal cytology, Muscle, Skeletal metabolism, Osteocalcin genetics, Osteocalcin metabolism, Peptides chemistry, Peptides genetics, Rats, Rats, Wistar, Stem Cells cytology, X-Ray Diffraction, Bone Morphogenetic Proteins metabolism, Bone and Bones metabolism, Epitopes, Peptides metabolism, Stem Cells physiology, Transforming Growth Factor beta
- Abstract
Bone morphogenetic protein-2 (BMP-2) promotes the formation and regeneration of bone and cartilage, and also participates in organogenesis, cell differentiation, cell proliferation, and apoptosis. BMP-2 has two epitopes referred to as the "wrist epitope" and the "knuckle epitope". The wrist epitope is thought to bind to BMP receptor IA and the knuckle epitope to BMP receptor type II. However, the precise receptor-binding region in BMP-2 has not yet been clarified. Here, we report that a synthetic peptide, KIPKASSVPTELSAISTLYL, corresponding to residues 73-92 of the knuckle epitope of BMP-2, elevated alkaline phosphatase (ALP) activity in the murine multipotent mesenchymal cell line, C3H10T1/2. The 73-92 peptide significantly inhibited the binding of rhBMP-2 to both BMP receptors type IA and type II. The 73-92 peptide also promoted the expression of osteocalcin mRNA and induced ectopic calcification when it was immobilized on a covalently cross-linked alginate gel and implanted into rat calf muscle. The X-ray diffraction (XRD) pattern of the calcified product was identical to that of the rat tibia, and the major peaks were attributed to hydroxyapatite. These results indicate that the 73-92 peptide may be one of the receptor-binding sites on BMP-2 and may stimulate bone precursor cells to induce calcification.
- Published
- 2003
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