title: The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis.
abstract: The presence of heparin binding has been become crucial in exerting growth factor related tissue formation. Receptor-mediated osteoblastic differentiation by bone morphogenetic protein (BMP)-4 and supportive function of its heparin binding has been proposed, direct role of the heparin binding site of BMP-4 on osteogenesis has not yet been fully investigated. If the binding site itself plays role on osteogenesis, the site domain can be useful in bone formation in combination with biomaterial. Herein, we synthesized a peptide sequence corresponding to residues 15-24 of BMP-4 (HBD, RKKNPNCRRH), as potential heparin binding sequence. The HBD peptide-induced ostoegenic differentiation by activating extracellular signal-regulated kinase (ERK1/2), one of the key regulators in hMSC. Also, treatment of cultured hMSCs with heparinase blocked both HBD peptide-induced osteogenic differentiation and GAG chain detection while abolishing the increased phospho-ERK level. These results suggest that the identified heparin binding domain peptide (HBD) stimulated osteoblastic differentiation via interaction with heparin and the ERK signaling. In vivo results further demonstrated that HBD, as a form of complex with alginate gel, was able to induce bone formation in the bone defect.
authors.affiliation: School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jue Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Jun Beom
authors.initials: JB
authors.lastname: Park
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Suh
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Choi
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chong-Pyoung
authors.initials: CP
authors.lastname: Chung
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006493:Heparin / Q000235:genetics / Q000378:metabolism*; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D004791:Enzyme Inhibitors; D010455:Peptides; D006493:Heparin; D019763:Heparin Lyase