Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration.
Combinatorial gene therapy with BMP2/7 enhances cranial bone regeneration.
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DOI：
10.1177/154405910808700906
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发表时间：
2008-09
影响因子：
7.6
通讯作者：
Franceschi, R. T.
中科院分区：
文献类型：
--
作者：
Koh, J. T.;Zhao, Z.;Wang, Z.;Lewis, I. S.;Krebsbach, P. H.;Franceschi, R. T.
腺病毒表达BMP2/7异二聚体可刺激皮下骨形成。在本研究中，我们评估这种方法是否也会促进颅骨缺损的愈合。表达BMP2或BMP7 （AdBMP2, AdBMP7）的腺病毒在转导到小鼠BLK细胞后，被滴定以产生相等的BMP蛋白水平。条件培养基分析表明，相对于等量的BMP2或BMP7同型二聚体，BMP2/7异源二聚体刺激碱性磷酸酶和Smad 1、5、8磷酸化的能力增强。为了测量骨再生，我们将病毒转导的BLK细胞植入C57BL6小鼠产生的临界大小的颅骨缺损中。与AdBMP2或BMP7单独转导的细胞相比，AdBMP2/7转导的细胞在修复颅骨缺损方面更有效。显微ct显示骨体积分数显著增加，再生骨与缺损边缘融合。因此，利用基因疗法表达异二聚体bmp是治疗颅面骨的一种很有前途的潜在疗法。
BMP2/7 heterodimer expression by adenovirus can stimulate bone formation at subcutaneous sites. In the present study, we evaluate whether this approach will also promote healing of cranial defects. Adenovirus expressing BMP2 or BMP7 (AdBMP2, AdBMP7) was titrated to yield equivalent BMP protein levels after transduction into murine BLK cells. Analysis of conditioned medium showed that BMP2/7 heterodimers have enhanced ability to stimulate alkaline phosphatase and Smad 1,5,8 phosphorylation relative to equivalent amounts of BMP2 or BMP7 homodimers. To measure bone regeneration, we implanted virally transduced BLK cells into critical-sized calvarial defects generated in C57BL6 mice. AdBMP2/7-transduced cells were more effective in healing cranial defects than were cells individually transduced with AdBMP2 or BMP7. Dramatic increases in bone volume fraction, as measured by microCT, as well as fusion of regenerated bone with the defect margins were noted. Thus, the use of gene therapy to express heterodimeric BMPs is a promising potential therapy for healing craniofacial bones.
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影响因子：
7.6
作者：
King, GN;King, N;Hughes, FJ
通讯作者：
Hughes, FJ
影响因子：
4.2
作者：
Riew, KD;Wright, NM;Lou, J
通讯作者：
Lou, J
DOI：
10.1006/bbrc.1995.1712
发表时间：
1995-05-25
影响因子：
3.1
作者：
AONO, A;HAZAMA, M;FUJISAWA, Y
通讯作者：
FUJISAWA, Y
影响因子：
3.7
作者：
Nakamura, K;Shirai, T;Makishima, F
通讯作者：
Makishima, F
DOI：
10.1083/jcb.130.1.217
发表时间：
1995-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Yamashita H;ten Dijke P;Huylebroeck D;Sampath TK;Andries M;Smith JC;Heldin CH;Miyazono K
通讯作者：
Miyazono K