NPNT is Expressed by Osteoblasts and Mediates Angiogenesis via the Activation of Extracellular Signal-regulated Kinase.
NPNT is Expressed by Osteoblasts and Mediates Angiogenesis via the Activation of Extracellular Signal-regulated Kinase.
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NPNT由成骨细胞表达，并通过细胞外信号调节激酶的激活介导血管生成。
DOI：
10.1038/srep36210
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发表时间：
2016-10-26
影响因子：
4.6
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Kuek V;Yang Z;Chim SM;Zhu S;Xu H;Chow ST;Tickner J;Rosen V;Erber W;Li X;Qin A;Qian Y;Xu J
血管生成在骨发育和骨重建中起着重要作用，并由大量潜在的血管生成因子介导。然而，缺乏关于骨微环境中分泌的调节骨质疏松症的特定血管生成因子的数据。在这里，我们报告说，肾连蛋白（NPNT），表皮生长因子（EGF）重复超家族蛋白的成员和EGFL 6的同源物，在成骨细胞中表达。有趣的是，在切除卵巢的C57 BL/6 J小鼠和骨质疏松症患者的骨中，NPNT的基因表达减少。此外，还发现NPNT和CD 31的蛋白水平在OVX小鼠的胫骨中降低。外源性添加小鼠重组NPNT刺激内皮细胞迁移和管样结构形成此外，NPNT在离体胎鼠跖骨血管生成测定中促进血管生成。我们发现，NPNT刺激内皮细胞的细胞外信号调节激酶1/2（ERK 1/2）和p38丝裂原活化激酶（MAPK）的磷酸化。ERK 1/2的抑制削弱了NPNT诱导的内皮细胞迁移、管状结构形成和血管生成。总之，这些结果表明，NPNT是一种旁分泌血管生成因子，并可能在病理性骨质疏松症中发挥作用。这可能会为治疗骨骼疾病和损伤带来新的靶点。
Angiogenesis plays an important role in bone development and remodeling and is mediated by a plethora of potential angiogenic factors. However, data regarding specific angiogenic factors that are secreted within the bone microenvironment to regulate osteoporosis is lacking. Here, we report that Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of C57BL/6J ovariectomised mice and in osteoporosis patients. In addition, the protein levels of NPNT and CD31 are also found to be reduced in the tibias of OVX mice. Exogenous addition of mouse recombinant NPNT on endothelial cells stimulates migration and tube-like structure formation in vitro. Furthermore, NPNT promotes angiogenesis in an ex vivo fetal mouse metatarsal angiogenesis assay. We show that NPNT stimulates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated kinase (MAPK) in endothelial cells. Inhibition of ERK1/2 impaired NPNT-induced endothelial cell migration, tube-like structure formation and angiogenesis. Taken together, these results demonstrate that NPNT is a paracrine angiogenic factor and may play a role in pathological osteoporosis. This may lead to new targets for treatment of bone diseases and injuries.
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影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
DOI：
10.1007/978-1-61779-415-5_2
发表时间：
2012-01-01
期刊：
BONE RESEARCH PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Bakker, Astrid D.;Klein-Nulend, Jenneke
通讯作者：
Klein-Nulend, Jenneke
影响因子：
5.6
作者：
Chim, Shek Man;Kuek, Vincent;Xu, Jiake
通讯作者：
Xu, Jiake
影响因子：
2
作者：
JOYCE, NC;JOYCE, SJ;MEKLIR, B
通讯作者：
MEKLIR, B
影响因子：
20.3
作者：
Cackowski, Frank C.;Anderson, Judith L.;Roodman, G. David
通讯作者：
Roodman, G. David