TY - JOUR
T1 - Immobilized recombinant human bone morphogenetic protein-2 enhances the phosphorylation of receptor-activated Smads
AU - Yamachika, Eiki
AU - Tsujigiwa, Hidetsugu
AU - Shirasu, Nobuaki
AU - Ueno, Takaaki
AU - Sakata, Yoshirou
AU - Fukunaga, Joji
AU - Mizukawa, Nobuyoshi
AU - Yamada, Masao
AU - Sugahara, Toshio
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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.
AB - 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.
KW - Bone morphogenetic protein
KW - Immobilization
KW - Osteogenesis
KW - Phosphorylation
KW - Smad family
UR - http://www.scopus.com/inward/record.url?scp=60549100160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60549100160&partnerID=8YFLogxK
U2 - 10.1002/jbm.a.31833
DO - 10.1002/jbm.a.31833
M3 - Article
C2 - 18314893
AN - SCOPUS:60549100160
SN - 1549-3296
VL - 88
SP - 599
EP - 607
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
IS - 3
ER -