Neuroleukin/Autocrine Motility Factor Receptor Pathway Promotes Proliferation of Articular Chondrocytes through Activation of AKT and Smad2/3.
Neuroleukin/Autocrine Motility Factor Receptor Pathway Promotes Proliferation of Articular Chondrocytes through Activation of AKT and Smad2/3.
复制标题
神经白介素/自分泌运动因子受体途径通过激活 AKT 和 Smad2/3 促进关节软骨细胞增殖
DOI：
10.1038/srep15101
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发表时间：
2015-10-13
影响因子：
4.6
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Tian K;Zhong W;Zheng X;Zhang J;Liu P;Zhang W;Liu H
软骨缺损是一个临床疑难问题。由于软骨细胞增殖能力差，软骨修复的治疗策略远未达到最佳。自体软骨细胞植入是一种基于细胞的治疗方法，使用体外扩增的患者健康软骨细胞。然而，体外培养过程中软骨细胞去分化限制了其应用。神经白细胞素（NLK）是一种刺激细胞生长和迁移的多功能蛋白，与其受体自分泌运动因子受体（AMFR，也称为gp78）一起。我们研究了NLK和AMFR/gp78在体内软骨发育和体外培养关节软骨细胞中的表达，发现它们与软骨细胞的增殖和分化有关。当应用于分离的关节软骨细胞时，NLK促进细胞增殖和II型胶原的分泌，II型胶原是软骨细胞增殖的标志。进一步的研究表明，NLK上调pAKT和pSmad2/3，下调pSmad1/5。在动物实验中，NLK处理还能促进软骨细胞增殖，同时抑制终末分化，导致生长板区域增生区扩大，但肥厚前区和肥厚区减少。因此，NLK是一种候选因子，可以应用于软骨缺损的治疗。
Cartilage defect is an intractable clinical problem. Therapeutic strategies for cartilage repair are far from optimal due to poor proliferation capacity of chondrocytes. Autologous chondrocyte implantation is a cell based therapy that usesin vitroamplified healthy chondrocytes from the patient. However, chondrocyte dedifferentiation duringin vitroculture limits its application. Neuroleukin (NLK) is a multifunctional protein that stimulates cell growth and migration, together with its receptor autocrine motility factor receptor (AMFR, also called gp78). We investigated expression of NLK and AMFR/gp78 during cartilage developmentin vivoand in cultured articular chondrocytesin vitroand found the pair associates with chondrocyte proliferation and differentiation. While applied to isolated articular chondrocytes, NLK promotes cell proliferation and secretion of type II collagen, a marker of proliferating chondrocytes. Further work demonstrates that NLK up regulates pAKT and pSmad2/3, but down regulates pSmad1/5. In animals, NLK treatment also promotes chondrocyte proliferation while inhibits terminal differentiation, leading to expanded proliferating zone but decreased prehypertrophic and hypertrophic zones in the growth plate region. NLK is therefore a candidate factor that can be applied in the treatment of cartilage defects.