Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis.
Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis.
复制标题
血管组织是在分散骨质发生引起的骨形成过程中BMP2表达的主要来源。
DOI：
10.1016/j.bone.2012.02.017
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发表时间：
2012-07
期刊：
影响因子：
4.1
通讯作者：
Gerstenfeld, Louis C.
中科院分区：
文献类型：
--
作者：
Matsubara, Hidenori;Hogan, Daniel E.;Morgan, Elise F.;Mortlock, Douglas P.;Einhorn, Thomas A.;Gerstenfeld, Louis C.
关键词：
先前的研究表明，牵张成骨（DO）过程中的骨再生依赖于血管组织的发育，抑制VEGFR信号会降低BMP2的表达。采用微计算机断层扫描（μCT）、BMP2编码区插入β-半乳糖苷酶的BAC转基因小鼠的免疫组织学和组织学分析以及qRT-PCR分析相结合的方法，研究了DO过程中驱动骨骼和维管组织发育的形态发生信号的时空协调表达。结果表明，BMP2在平滑肌和动脉静脉血管内皮细胞、毛细血管内皮细胞、增生性软骨细胞和骨细胞中均被诱导表达。淋巴管和噬菌体均未表达BMP2。BMP2 mRNA在周围肌肉组织和牵张间隙中分别表达，并首先与大血管侧支和小动脉重构相对应，然后是间隙区域的血管新生期。VEGF受体和配体的免疫组织学和qRT-PCR分析显示，间充质细胞、衬细胞和软骨细胞均表达VEGFA，但PlGF仅在间隙区间充质细胞中表达。另一方面，VEGFR2似乎主要在血管内皮细胞和造血细胞中表达。这些结果表明，骨和维管组织的形成是通过一组相互支持的旁分泌环来协调的，其中血管主要合成促进骨形成的形成因子，而间充质细胞主要合成促进维管组织形成的形成因子。
Prior studies showed that bone regeneration during distraction osteogenesis (DO) was dependent on vascular tissue development and that inhibition of VEGFR signaling diminished the expression of BMP2. A combination of micro-computed tomography (μCT) analysis of vascular and skeletal tissues, immunohistological and histological analysis of transgenic mice containing a BAC transgene in which β-galactosidase had been inserted into the coding region of BMP2 and qRT-PCR analysis, were used to examine how the spatial temporal expression of the morphogenetic signals that drive skeletal and vascular tissue development are coordinated during DO. These results showed BMP2 expression was induced in smooth muscle and vascular endothelial cells of arteries and veins, capillary endothelial cells, hypertrophic chondrocytes and osteocytes. BMP2 was not expressed by lymphatic vessels or marcophages. Separate peaks of BMP2 mRNA expression were induced in the surrounding muscular tissues and the distraction gap and corresponded first with large vessel collateralization and arteriole remodeling followed by periods of angiogenesis in the gap region. Immunohistological and qRT-PCR analysis of VEGF receptors and ligands showed that mesenchymal cells, lining cells and chondrocytes, expressed VEGFA, although PlGF expression was only seen in mesenchymal cells within the gap region. On the other hand VEGFR2 appeared to be predominantly expressed by vascular endothelia and hematopoietic cells. These results suggest that bone and vascular tissue formation is coordinated via a mutually supporting set of paracrine loops in which blood vessels primarily synthesize the morphogens that promote bone formation while mesenchymal cells primarily synthesize the morphogens that promote vascular tissue formation.
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DOI：
10.1016/j.pathophys.2009.10.004
发表时间：
2010-09-01
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Bahram, Fuad;Claesson-Welsh, Lena
通讯作者：
Claesson-Welsh, Lena
影响因子：
2.5
作者：
Alva, JA;Zovein, AC;Iruela-Arispe, ML
通讯作者：
Iruela-Arispe, ML
影响因子：
4.1
作者：
Bais, M. V.;Wigner, N.;Young, M.;Toholka, R.;Graves, D. T.;Morgan, E. F.;Gerstenfeld, L. C.;Einhorn, T. A.
通讯作者：
Einhorn, T. A.
影响因子：
3.7
作者：
Coso, Sanja;Zeng, Yiping;Williams, Elizabeth D.
通讯作者：
Williams, Elizabeth D.
DOI：
10.1016/j.bbrc.2004.05.181
发表时间：
2004-07-23
影响因子：
3.1
作者：
Cola, C;Almeida, M;Mehta, JL
通讯作者：
Mehta, JL