Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling.
Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling.
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DOI：
10.1242/bio.20134986
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发表时间：
2013
期刊：
影响因子：
2.4
通讯作者：
Durrieu MC
中科院分区：
文献类型：
--
作者：
Zouani OF;Rami L;Lei Y;Durrieu MC
成熟成骨细胞是负责骨形成的细胞，来源于前体细胞成骨细胞。然而，控制这种分化的机制却知之甚少。事实上，人体的大多数器官都是由“软”组织组成的，细胞很容易从“软”组织中分离出来并进行研究，而骨的“硬”矿化组织使研究骨细胞的功能变得困难。在这里，我们建立了一个体外模型来模拟生理条件下的这种分化。我们获得了成熟的成骨细胞，并根据以下参数对其进行了表征：成骨细胞标志物如Runx2和col - 1的强烈表达；实现特定尺寸（细胞体积比成骨细胞前体增加26倍）；并产生大量的细胞外基质，也称为类骨。我们证明了成骨细胞前体向成熟成骨细胞的分化需要骨形态发生蛋白（BMP）受体的持续激活，我们将BMP-2模拟肽固定在模拟体内微环境的合成基质上。重要的是，我们证明了细胞的f -肌动蛋白网络和乙酰化微管的组织在分化过程中被修饰。我们发现f -肌动蛋白细胞骨架组织的扰动取消了分化过程。此外，我们证明了Runx2基因的表达是这种分化所必需的。这些发现证明了由于BMP-2的持续诱导而对细胞质和基因成分进行了反向调节，并为骨组织中bmp的正确信号传导提供了更详细的见解。
Mature osteoblasts are the cells responsible for bone formation and are derived from precursor osteoblasts. However, the mechanisms that control this differentiation are poorly understood. In fact, unlike the majority of organs in the body, which are composed of “soft” tissue from which cells can easily be isolated and studied, the “hard” mineralized tissue of bone has made it difficult to study the function of bone cells. Here, we established an in vitro model that mimics this differentiation under physiological conditions. We obtained mature osteoblasts and characterized them on the basis of the following parameters: the strong expression of osteoblastic markers, such as Runx2 and Col-I; the achievement of specific dimensions (the cell volume increases 26-fold compared to the osteoblast precursors); and the production of an abundant extracellular matrix also called osteoid. We demonstrated that the differentiation of osteoblast precursors into mature osteoblasts requires the continuous activation of Bone Morphogenetic Protein (BMP) receptors, which we established with the immobilization of a BMP-2mimetic peptide on a synthetic matrix mimicking in vivo microenvironment. Importantly, we demonstrated that the organization of the F-actin network and acetylated microtubules of the cells were modified during the differentiation process. We showed that the perturbation of the F-actin cytoskeleton organization abolished the differentiation process. In addition, we demonstrated that expression of the Runx2 gene is required for this differentiation. These findings demonstrate the retro-regulation of cytoplasmic and genic components due to the continuous induction of BMP-2 and also provide more detailed insights into the correct signaling of BMPs for cell differentiation in bone tissue.
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DOI：
10.1016/j.bioeng.2007.07.012
发表时间：
2007-11-01
期刊：
BIOMOLECULAR ENGINEERING
影响因子：
--
作者：
Chollet, C.;Chanseau, C.;Durrieu, M. C.
通讯作者：
Durrieu, M. C.
影响因子：
3.7
作者：
Hancock R;Hadj-Sahraoui Y
通讯作者：
Hadj-Sahraoui Y
影响因子：
6.2
作者：
Kato, Y;Boskey, K;Bonewald, LF
通讯作者：
Bonewald, LF
影响因子：
3.2
作者：
GOHEL, AR;HAND, AR;GRONOWICZ, GA
通讯作者：
GRONOWICZ, GA
影响因子：
6.2
作者：
Monfoulet, Laurent-Emmanuel;Rabier, Benedicte;Chassande, Olivier
通讯作者：
Chassande, Olivier