Synthetic peptide-coated bone mineral for enhanced osteoblastic activation in vitro and in vivo.
A 15-mer synthetic peptide, designated P1, was derived from the bone morphogenetic protein (BMP) receptor I and BMP receptor II binding domains of BMP-2 for the purpose of enhancing bone regeneration capacity of inorganic bovine bone mineral. A second peptide, denoted P2, was designed by adding seven glutamic acid residues to the N-terminal of P1 to increase the surface coating efficiency onto bone mineral. The coating efficiency of P1 increased with the concentration of peptide. P2 peptide, in contrast, had a higher coating efficiency at lower peptide concentrations. The peptides properly transduced intracellular signals properly via the Smad and ERK pathways, thereby increasing mineralization in vitro, implying that the peptides alone can induce osteoblastic differentiation. Adhesion of cells to bone mineral was greater when peptides were present than in bone mineral alone. P1- and P2-coated bone mineral increased osteoblastic differentiation, as demonstrated by ALPase activity. P1-coated bone mineral stimulated more new bone regeneration in bone defect sites after 2 weeks than the peptide-free control. These peptides, in combination with bone grafts or implants, have the potential to enhance osteoblastic differentiation and bone regeneration.
Lee
Jue-Yeon
JY
Intellectual Biointerface Engineering Center (IBEC), College of Dentistry, Seoul National University,Seoul, South Korea.
Choo
Jung-Eun
JE
Park
Hyun-Jung
HJ
Park
Jun-Bum
JB
Lee
Sang-Chul
SC
Lee
Seung-Jin
SJ
Park
Yoon-Jeong
YJ
Chung
Chong-Pyoung
CP
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
D018786:Bone Substitutes; D020099:Coated Materials, Biocompatible; D010455:Peptides; D051785:Smad Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D052004:Bone Morphogenetic Protein Receptors