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

Yoon Jung Choi, Jue Yeon Lee, Jung Hyun Park, Jun Beom Park, Jin Sook Suh, Young Suk Choi, Seung Jin Lee, Chong Pyoung Chung, Yoon Jeong Park

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish
Pages (from-to)7226-7238
Number of pages13
JournalBiomaterials
Volume31
Issue number28
DOIs
StatePublished - Oct 2010

Keywords

  • Bioactive material
  • Bone formation
  • Bone morphogenetic protein-4
  • ERK1/2 pathway
  • Heparin binding domain (HBD) peptide
  • Osteoblastic differentiation

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