BMP2 is essential for post natal osteogenesis but not for recruitment of osteogenic stem cells.
BMP2 is essential for post natal osteogenesis but not for recruitment of osteogenic stem cells.
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DOI：
10.1016/j.bone.2009.04.239
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发表时间：
2009-08
期刊：
影响因子：
4.1
通讯作者：
Einhorn, T. A.
中科院分区：
文献类型：
--
作者：
Bais, M. V.;Wigner, N.;Young, M.;Toholka, R.;Graves, D. T.;Morgan, E. F.;Gerstenfeld, L. C.;Einhorn, T. A.
用C57BL/6J(B6)小鼠观察BMP2对骨髓去除后骨髓基质细胞分化和骨形成的影响。慢病毒BMP2 shRNA抑制BMP2的表达可阻止体外矿化结节的形成和体内的骨形成，并阻断成骨分化的转录决定因子Runx2和Osterix的表达。对转录因子Sox9的表达没有影响，Sox9是第一个在承诺的软骨祖细胞和骨祖细胞中表达的转录决定因素之一。体外研究表明，外源添加BMP7可以挽救Osterix的表达，增强Sox9的表达，但对Runx2的表达没有影响，只是部分恢复了培养物中矿物质沉积的发育。另一方面，外源BMP2的加入挽救了Runx2和Osterix的表达，但没有增强Sox9的表达，但完全恢复了对培养物中矿物质沉积的抑制。使用针对CD146和Sox9的抗体，对骨髓切除三天后在骨髓间隙中发现的细胞群的免疫组织学检查显示，在对照组和BMP2 shRNA处理的动物中，表达这些骨骼祖细胞和干细胞标记物的细胞数量相同。用CD146抗体对去髓后3天骨髓腔内发现的细胞进行荧光激活细胞分类(FACS)分析，结果显示对照组和shRNA处理组的免疫阳性细胞数基本相同。综上所述，体外观察到BMP2和BMP7在成骨基因表达和矿化方面的差异表明它们在骨细胞分化中具有不同的作用。这些结果进一步证明，在体内，BMP2是出生后骨祖细胞分化的中枢形态发生调节因子，但不影响祖细胞向成骨细胞谱系的招募。
The effects of BMP2 on bone marrow stromal cell differentiation and bone formation after bone marrow ablation were determined using C57 BL/6J (B6) mice. Inhibition of BMP2 expression with lentiviral BMP2 shRNA prevented both mineralized nodule formation in vitro and bone formation in vivo, and blocked the expression of Runx2 and osterix, transcriptional determinants of terminal osteogenic differentiation. No effect was observed on the expression of Sox9, a transcription factor, which is the one of the first transcriptional determinant to be expressed in committed chondroprogenitor and osteoprogenitor cells. In vitro studies showed that exogenously added BMP7 rescued the expression of osterix and enhanced the expression of Sox9, but had no effect on the expression of Runx2, while it only partially recovered the development of mineral deposition in the cultures. On the other hand, the exogenous addition of BMP2 rescued both Runx2 and osterix expression, did not enhance the expression of Sox9, but fully recovered the inhibition of mineral deposition in the cultures. Using antibodies against CD146 and Sox9, immunohistological examination of the cell populations found in the medullary space three days after bone marrow ablation, showed qualitatively equal numbers of cells expressing these skeletal progenitor and stem cell markers in control and BMP2 shRNA-treated animals. Fluorescence Activated Cell Sorting (FACS) analysis of the cells found with the marrow cavities at three days after marrow ablation using CD146 antibody showed near equal numbers of immunopositive cells in both control and shRNA treated animals. In summary, the differences observed in vitro for BMP2 and BMP7 on osteogenic gene expression and mineralization suggest that they have differing effects on bone cell differentiation. These results further demonstrate that in vivo BMP2 is a central morphogenetic regulator of post natal osteoprogenitor differentiation, but does not affect recruitment of progenitors to the osteoblastic lineage.
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影响因子：
4.8
作者：
Celil, AB;Campbell, PG
通讯作者：
Campbell, PG
影响因子：
5.1
作者：
Betz, O. B.;Betz, V. M.;Evans, C. H.
通讯作者：
Evans, C. H.
影响因子：
6.2
作者：
Okamoto, Mina;Murai, Junko;Tsumaki, Noriyuki
通讯作者：
Tsumaki, Noriyuki
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
12.4
作者：
Gambaro, K.;Aberdam, E.;Rouleau, M.
通讯作者：
Rouleau, M.