Guided tissue regeneration with immobilized cytokine

用固定化细胞因子引导组织再生

• 批准号: 16591996
• 负责人: YAMACHIKA Eiki
• 金额: $ 2.24万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591996/
• 关键词: BMP; Cytokine; Immobilization; bone; Regeneration; BMP-2; I型アテロコラーゲン; 細胞活性; 細胞内シグナル伝達; Smad

Bone morphogenetic protein 2(BMP-2) plays an important role in bone growth and regeneration. The creation of purified recombinant human BMP-2 (rhBMP-2) has led to advances in its potential for clinical use, however this protein is soluble and disperses soon after implantation. So rhBMP-2 can't have long time stimulation to BMP signaling cascade. To overcome this problem we reported the effects of immobilization of rhBMP-2 to succinylated type I atelocollagenThe mechanism of immobilized rhBMP-2 is based on the theories of covalent bonding between rhBMP-2 and succinylated type I atelocollagen. The immobilized rhBMP-2 binds with the receptor on the cell surface without being internalized into the cell, so it is able to transduce signals into the cell over a long period of time, achieving high efficiency in promoting cell proliferation.We investigated the effect of immobilized rhBMP-2 by the way of (a) histological findings, (b) alkaline phosphatase (ALP) activity, (c) BMP intracellular signaling cascade (Smad1, Smad5 and phospho Smad1/5/8) expression, and (d) type I collagen, osteonectin, osteopontin, ostocalcin, and Smad1/5/8 mRNA expression.Our results showed that (1) nonimmobilized and immobilized rhBMP-2 also increased the alkaline phosphatase (ALP) activity in ST2, MC3T3 and C2C12 cells. However significantly higher ALP activity was observed by the immobilized rhBMP-2 treatment. (2) Phosphorylation of Smad1/5/8 after nonimmobilized rhBMP-2 stimulation increased from 15 min after stimulation and decrease to the control revel after 6hrs, however the phosphorylation was prolonged by immobilized rhBMP-2 and its effect was detectable even after 48hrs.So we conclude that because immobilized rhBMP-2 can emphasize and prolonged the effect of rhBMP-2, immobilizing rhBMP-2 is an efficient method to increase bone induction.

骨形态发生蛋白2（BMP-2）在骨骼生长和再生中起重要作用。纯化的重组人BMP-2（RHBMP-2）的创建导致其临床使用的潜力取得了进步，但是该蛋白质可溶并在植入后不久分散。因此，RHBMP-2不能长时间刺激BMP信号级联。为了克服这个问题，我们报道了RHBMP-2固定对I型琥珀酰化I型固定的RHBMP-2机制的影响是基于RHBMP-2和I型I型I atelocollagen之间共价键合的理论。 The immobilized rhBMP-2 binds with the receptor on the cell surface without being internalized into the cell, so it is able to transduce signals into the cell over a long period of time, achieving high efficiency in promoting cell proliferation.We investigated the effect of immobilized rhBMP-2 by the way of (a) histological findings, (b) alkaline phosphatase (ALP) activity, (c) BMP intracellular signaling Cascade（SMAD1，SMAD5和Phospho SMAD1/5/8）表达，（D）I型胶原蛋白，骨to蛋白，骨teopontin，Osteopontin，ostocalcalcin和Smad1/5/8 mRNA表达。 C2C12细胞。然而，通过固定的RHBMP-2处理观察到了明显更高的ALP活性。 （2）在非刺激RHBMP-2刺激后SMAD1/5/8的磷酸化从刺激后的15分钟开始增加并减少6小时后的控制启动，但是磷酸化延长了固定的RHBMP-2，即使在48小时后仍能检测到它的效应，因此我们的效果也可以结束，因为我们结束了效应，因为Immby and-nized and ump-2 pans and and-2-2均为2-2固定RHBMP-2是增加骨诱导的有效方法。

项目成果

Effects of immobilized recombinant human bone morphogenetic protein-2/succinylated type I atelocollagen on cellular activity of ST2 cells

• DOI: 10.1002/jbm.a.30416
• 发表时间: 2005-10-01
• 期刊: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
• 影响因子: 4.9
• 作者: Tsujigiwa, H;Nagatsuka, H;Nagai, N
• 通讯作者: Nagai, N

Immobilized rhBMP-2/succinylated type I atelocollagen gene expression of intracellular signaling molecules on ST2 cells.

ST2 细胞上细胞内信号分子的固定化 rhBMP-2/琥珀酰化 I 型去端胶原基因表达。

• 发表时间: 2006
• 期刊: J Biomed Mater Res A. 77(3)
• 作者: Tsukuba;T. et al.;Tsujigiwa H
• 通讯作者: Tsujigiwa H

Genetic and epigenetic alterations of BRG1 promote oral cancer development.

• DOI: 10.3892/ijo.26.1.201
• 发表时间: 2005
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: E. Gunduz;M. Gunduz;M. Ouchida;H. Nagatsuka;L. Beder;H. Tsujigiwa;K. Fukushima;K. Nishizaki;K. S

Osteogenic potential of periosteum graft in the rat calvarial model

大鼠颅骨模型中骨膜移植物的成骨潜力

• 发表时间: 2005
• 期刊: Ann Plast Surg 54(1)
• 作者: Cui Z.-G.;et al.;K.NAGATA et al.;Takeda Y;Yamachika E;Mizukawa N;山村 功ら;Tsujigiwa H;Fukunaga J
• 通讯作者: Fukunaga J

Expression of osteoclast differentiation factor and ostelclastogenesis inhibitory factor in rat osteoporosis induce by immunosuppressant FK506.

免疫抑制剂FK506诱导大鼠骨质疏松中破骨细胞分化因子和破骨细胞生成抑制因子的表达

• 发表时间: 2004
• 期刊: Bone. 34(3)
• 作者: Cui Z.-G.;et al.;K.NAGATA et al.;Takeda Y;Yamachika E;Mizukawa N;山村 功ら;Tsujigiwa H;Fukunaga J;Takagi S;Nagatsuka H;Takagi S;Nobuhisa T;Nobuyoshi Mizukawa;Yamachika E;植野高章;Fukunaga J;Shin Takagi;Fukunaga J
• 通讯作者: Fukunaga J