The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis

被引:51
作者
Choi, Yoon Jung [2 ]
Lee, Jue Yeon [2 ,4 ]
Park, Jung Hyun [1 ,2 ]
Park, Jun Beom [1 ,2 ]
Suh, Jin Sook [2 ]
Choi, Young Suk [2 ]
Lee, Seung Jin [3 ]
Chung, Chong-Pyoung [1 ,2 ,4 ]
Park, Yoon Jeong [1 ,2 ,4 ]
机构
[1] Seoul Natl Univ, Sch Dent, Dept Periodontol, Seoul 110749, South Korea
[2] Seoul Natl Univ, Dent Res Inst, Seoul 110749, South Korea
[3] Ewha Womans Univ, Coll Pharm, Dept Ind Pharm, Seoul, South Korea
[4] Nano Intelligent Biomed Engn Corp NIBEC, Res Ctr, Seoul, South Korea
关键词
Heparin binding domain (HBD) peptide; Bone morphogenetic protein-4; Osteoblastic differentiation; ERK1/2; pathway; Bioactive material; Bone formation; FIBROBLAST-GROWTH-FACTOR; OSTEOBLASTIC DIFFERENTIATION; CELL-DIFFERENTIATION; IN-VITRO; KINASE; FIBRONECTIN; ACTIVATION; RECEPTOR; SULFATE; BMP-2;
D O I
10.1016/j.biomaterials.2010.05.022
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7226 / 7238
页数:13
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