Persistent Sox9 expression in hypertrophic chondrocytes suppresses transdifferentiation into osteoblasts.
Persistent Sox9 expression in hypertrophic chondrocytes suppresses transdifferentiation into osteoblasts.
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DOI：
10.1016/j.bone.2019.05.027
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发表时间：
2019-08
期刊：
影响因子：
4.1
通讯作者：
Baron J
中科院分区：
文献类型：
--
作者：
Lui JC;Yue S;Lee A;Kikani B;Temnycky A;Barnes KM;Baron J
纵向骨生长是由软骨内骨化驱动的，软骨内骨化是一个软骨组织由生长板软骨细胞产生，然后由成骨细胞重塑成骨的过程。在出生后的生长板中，随着肥大的软骨细胞接近软骨-骨结合部，它们可能经历凋亡，或直接转分化成成骨细胞。控制这种细胞谱系转换的分子机制知之甚少。在这里，我们表明，Sox 9在肥大的软骨细胞中的生理下调与成骨细胞相关基因（如Mmp 13，Cola 1，Ibsp）在肥大的软骨细胞中的上调，在他们进入干骺端骨。在转基因小鼠中，继续表达Sox 9的所有细胞来源于软骨细胞谱系，上调这些成骨细胞相关基因在肥大区未能发生。此外，谱系追踪实验表明，在表达Sox 9的转基因小鼠中，软骨细胞转分化为成骨细胞的数量显着减少。总的来说，我们的研究结果表明，Sox 9在肥大软骨细胞中的下调促进肥大软骨细胞中成骨细胞相关基因的表达，并促进这些细胞随后转分化为成骨细胞。
Longitudinal bone growth is driven by endochondral ossification, a process in which cartilage tissue is generated by growth plate chondrocytes and then remodeled into bone by osteoblasts. In the postnatal growth plate, as hypertrophic chondrocytes approach the chondro-osseous junction, they may undergo apoptosis, or directly transdifferentiate into osteoblasts. The molecular mechanisms governing this switch in cell lineage are poorly understood. Here we show that the physiological downregulation of Sox9 in hypertrophic chondrocyte is associated with upregulation of osteoblast-associated genes (such as Mmp13, Cola1, Ibsp) in hypertrophic chondrocytes, before they enter the metaphyseal bone. In transgenic mice that continued to express Sox9 in all cells derived from the chondrocytic lineage, upregulation of these osteoblast-associated genes in the hypertrophic zone failed to occur. Furthermore, lineage tracing experiments showed that, in transgenic mice expressing Sox9, the number of chondrocytes transdifferentiating into osteoblasts was markedly reduced. Collectively, our findings suggest that Sox9 downregulation in hypertrophic chondrocytes promotes expression of osteoblast-associated genes in hypertrophic chondrocytes and promotes the subsequent transdifferentiation of these cells into osteoblasts.
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影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
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：
7
作者：
Ahmed, Y. A.;Tatarczuch, L.;Mackie, E. J.
通讯作者：
Mackie, E. J.
影响因子：
3.7
作者：
Oh CD;Lu Y;Liang S;Mori-Akiyama Y;Chen D;de Crombrugghe B;Yasuda H
通讯作者：
Yasuda H
影响因子：
4.1
作者：
Lui, Julian C. K.;Andrade, Anenisia C.;Forcinito, Patricia;Hegde, Anita;Chen, WeiPing;Baron, Jeffrey;Nilsson, Ola
通讯作者：
Nilsson, Ola