The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis.
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.
Choi
Yoon Jung
YJ
School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.
Lee
Jue Yeon
JY
Park
Jung Hyun
JH
Park
Jun Beom
JB
Suh
Jin Sook
JS
Choi
Young Suk
YS
Lee
Seung Jin
SJ
Chung
Chong-Pyoung
CP
Park
Yoon Jeong
YJ
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
D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D004791:Enzyme Inhibitors; D010455:Peptides; D006493:Heparin; D019763:Heparin Lyase