Immobilized rhBMP-2/succinylated type I atelocollagen gene expression of intracellular signaling molecules on ST2 cells.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) chemically-bonded to succinylated type I atelocollagen, a biomaterial carrier with a porous structure, was reported to augment cellular activity of ST2 cells. The Smad protein family has been suggested to play an important role in the intracellular signaling pathway of BMP by its binding to receptors on target cells. However, there has been no study analyzing the downstream genes of the rhBMP-2 induced intracellular signal transduction pathway. The purpose of this study was to examine the effect of immobilized rhBMP-2 on gene expression of intracellular signaling molecules on ST2 cells. Our study showed two expression patterns of downstream genes of rhBMP-2 intracellular signal transduction pathway. In the first pattern, BMPR-IA, Smad 1, and Smad 5 genes showed high basic expression before the addition of rhBMP, and the high level of gene expression continued for long period and decreased in the late stage when rhBMP-2 was immobilized. In the second pattern, Smad 6, Smad 7, and Smad 8 genes showed low basic expression before the addition of rhBMP-2 and a continuous increase from the beginning was followed by a decrease in the late stage when rhBMP-2 was immobilized. Our results also showed that intracellular signaling continued for prolonged period when rhBMP-2 was immobilized to succinylated type I atelocollagen. This study indicated that immobilizing rhBMP-2 is an efficient method to increase bone induction.
Department of Virology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Hidetsugu
H
Tsujigiwa
Hitoshi
H
Nagatsuka
You Jin
YJ
Lee
Phuu Pwint
PP
Han
Mehmet
M
Gunduz
Racquel Z
RZ
Legeros
Masahisa
M
Inoue
Masao
M
Yamada
Noriyuki
N
Nagai
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology*; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D051785:Smad Proteins / Q000096:biosynthesis / Q000235:genetics; D019802:Succinic Acid / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C059821:atelocollagen; D003094:Collagen; D019802:Succinic Acid