Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation
Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation
复制标题
DOI：
10.1016/j.bone.2015.06.023
复制
发表时间：
2015-12-01
期刊：
影响因子：
4.1
通讯作者：
Schindeler, Aaron
中科院分区：
文献类型：
--
作者：
Kolind, Mille;Bobyn, Justin D.;Schindeler, Aaron
为了更好地了解间充质细胞和内皮祖细胞在rhBMP-2诱导的骨形成中的相对作用，我们研究了Tie2-Cre：Ai9和αSMA-creERT2：Col2.3-GFP：Ai9报告小鼠中谱系标记细胞的分布。采用已建立的后肢和脊柱融合异位骨形成的骨科模型。Tie2系细胞广泛存在于异位骨和脊柱融合肿块中，但仅与抗酒石酸酸性磷酸酶(TRAP)活性(破骨细胞)和CD31免疫组织化学(血管内皮细胞)共染色，而碱性磷酸酶(AP)活性(成骨细胞)未见共染色。为了进一步证实Tie2系细胞对BMP诱导的骨缺乏功能的贡献，我们建立了条件基因敲除小鼠，其中Tie2系细胞对关键的骨转录因子osterix无效(Tie2-cre：OSX(FX/FX)小鼠)。条件基因敲除小鼠在BMP诱导的骨形成方面与小鼠对照组相比没有差异。在接受脊柱融合的小鼠中，用三苯氧胺对间充质细胞进行脉冲标记显示，阿尔法SMA系细胞对成骨细胞系(Col2.3-GFP)有贡献，但对内皮细胞或破骨细胞群没有贡献。这些数据表明，αSMA+和Tie2+祖细胞系在骨形成、血管生成和吸收/重塑过程中做出了不同的细胞贡献。皇冠版权所有(C)2015由爱思唯尔公司出版。保留所有权利。
To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and alpha SMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that alpha SMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the alpha SMA + and Tie2 + progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. Crown Copyright (C) 2015 Published by Elsevier Inc. All rights reserved.