Role of the protease corin in chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells.
Role of the protease corin in chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells.
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蛋白酶corin在人骨髓间充质干细胞软骨分化中的作用
DOI：
10.1002/term.2514
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发表时间：
2018-04
影响因子：
3.3
通讯作者：
Dong N
中科院分区：
文献类型：
--
作者：
Zhou H;Zhu J;Liu M;Wu Q;Dong N
Corin已在血管系统中进行了广泛的研究，并被认为可以调节血压。我们已经证明，corin是人类脂肪干细胞（hASC）成骨分化过程中最高度上调的基因之一。本研究验证了这一假设，通过调节血管生成信号通路，corin是成骨分化和软骨内骨化的关键调节因子。在体外，通过siRNA敲低抑制hASC中corin表达，并通过逆转录聚合酶链反应定量血管内皮生长因子A（VEGF-A）表达。在体内，使用鼠corin敲除模型（雌性，10周）来确定corin缺乏对长骨发育的影响。通过苏木精和伊红染色比较野生型和corin敲除长骨，以评估组织特征和细胞组织，通过三点弯曲评估力学特征，通过免疫组织化学观察VEGF-A表达模式。Corin敲低显著（p < 0.05）增加了成骨分化过程中VEGF-A mRNA的表达。在体内，corin基因敲除减少胫骨生长板厚度（p < 0.01），并严重减少肥大区域。Corin敲除股骨的刚度（p < 0.01）和最大载荷（p < 0.01）显著增加，但术后挠度降低（p < 0.01）。在corin基因敲除小鼠中，生长板附近的VEGF-A表达增加，但整个胫骨干和胫骨远端头的表达减少。这是第一项研究表明corin是通过调节VEGF-A表达来调节骨发育的关键调节因子。进一步阐明这一机制将有助于优化骨组织工程和再生医学疗法的发展。
Corin has been studied extensively within the vascular system and is known to regulate blood pressure. We have shown that corin is one of the most highly upregulated genes during osteogenic differentiation of human adipose‐derived stem cells (hASCs). This study tested the hypothesis that, through modulation of angiogenic signalling pathways, corin is a critical regulator of osteogenic differentiation and endochondral ossification. In vitro, corin expression in hASC was suppressed via siRNA knockdown and vascular endothelial growth factor A (VEGF‐A) expression was quantified via reverse transcription polymerase chain reaction. In vivo, a murine corin knockout model (female, 10 weeks) was used to determine the effect of corin deficiency on long bone development. Wild‐type and corin knockout long bones were compared via haematoxylin and eosin staining to assess tissue characteristics and cellular organization, three‐point bending to assess mechanical characteristics, and immunohistochemistry to visualize VEGF‐A expression patterns. Corin knockdown significantly (p < 0.05) increased VEGF‐A mRNA expression during osteogenic differentiation. In vivo, corin knockout reduced tibial growth plate thickness (p < 0.01) and severely diminished the hypertrophic region. Corin knockout femurs had significantly increased stiffness (p < 0.01) and maximum loads (p < 0.01) but reduced postyield deflections (p < 0.01). In corin knockout mice, VEGF‐A expression was increased near the growth plate but was reduced throughout the tibial shaft and distal head of the tibiae. This is the first study to show that corin is a key regulator of bone development by modulation of VEGF‐A expression. Further elucidation of this mechanism will aid in the development of optimized bone tissue engineering and regenerative medicine therapies.
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Corin 和心钠素在人肾段表达的定位
DOI：
10.1042/cs20160398
发表时间：
2016-09-01
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Dong L;Wang H;Dong N;Zhang C;Xue B;Wu Q
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0407234102
发表时间：
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影响因子：
11.1
作者：
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DOI：
10.1161/circheartfailure.109.866822
发表时间：
2009-11
期刊：
Circulation. Heart failure
影响因子：
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作者：
Rame JE;Tam SW;McNamara D;Worcel M;Sabolinski ML;Wu AH;Dries DL
通讯作者：
Dries DL
影响因子：
4.8
作者：
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