Immobilized recombinant human bone morphogenetic protein-2 enhances the phosphorylation of receptor-activated Smads

Eiki Yamachika, Hidetsugu Tsujigiwa, Nobuaki Shirasu, Takaaki Ueno, Yoshirou Sakata, Joji Fukunaga, Nobuyoshi Mizukawa, Masao Yamada, Toshio Sugahara

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Bone morphogenetic protein (BMP)-2 plays an important role in bone growth and regeneration; however, BMP-2 is easily lost by diffusion through body fluid and has some inhibitory pathways. To address this problem, we previously immobilized recombinant human BMP-2 (rhBMP-2) on succi-nylated type I atelocollagen. Here, we examined the effect of immobilized rhBMP-2 in vitro and vivo. In ST2, MC3T3-E1, and C2C12 cells, alkaline phosphatase activity, which is a marker of osteoblast differentiation, was enhanced more by immobilized than nonimmobilized rhBMP-2. In addition, the phosphorylation of receptor-activated Smads, part of the sig-naling pathway activated by BMP-2, was prolonged by immobilized rhBMP-2 in these cells. Furthermore, implantation of immobilized rhBMP-2 into the backs of rats promoted the formation of mature bone-like structure. These results demonstrate that immobilized rhBMP-2 has higher bioactivity than nonimmobilized rhBMP-2, and, therefore, immobilization of rhBMP-2 can prolong BMP signaling.

Original languageEnglish
Pages (from-to)599-607
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume88
Issue number3
DOIs
Publication statusPublished - Mar 1 2009

Keywords

  • Bone morphogenetic protein
  • Immobilization
  • Osteogenesis
  • Phosphorylation
  • Smad family

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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