The use of mechano growth factor to prevent cartilagedegenerat ion in knee osteoarthritis

The use of mechano growth factor to prevent cartilagedegenerat ion in knee osteoarthritis
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使用机械生长因子预防膝骨关节炎软骨退变

DOI:
10.1002/term.2493
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发表时间:
2017
期刊:
J Tissue Eng Regen Med.
影响因子:
--
通讯作者:
Li Yang
Li Yang
中科院分区:
其他
文献类型:
--
作者:
Yang Song;Kang Xu;CanYu;Lili Dong;Peixing Chen;Yonggang Lv;MartinY.M. Chiang;Linhao Li;Liu Wanqian;Li Yang

文献摘要

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以往的研究更重视生长因子在软骨退变和骨关节炎(OA)治疗中的作用。本研究在体外和体内对机械生长因子- C24E (MGF)预防骨关节炎软骨退变的能力进行了评估。用10-60 ng/ml MGF处理体外培养的OA软骨细胞12小时,我们检测了OA软骨细胞的增殖、迁移和合成代谢。western blotting检测OA软骨细胞中转化生长因子β、SMAD家族成员3、缺氧诱导因子2α等未折叠蛋白的反应和OA病理特征。此外,通过小干扰RNA敲低蛋白激酶RNA样内质网激酶来阐明MGF治疗OA的潜在机制。在兔膝关节OA模型中,0.1-10 μg/ml MGF治疗2周后,软骨退变得到抑制。本研究表明MGF处理可以抑制OA软骨细胞的病理性凋亡,促进软骨细胞的增殖、迁移和基质合成。结果还表明,MGF治疗可以通过蛋白激酶RNA样内质网激酶调节的未折叠蛋白反应部分延缓OA软骨的退变,并提示MGF在OA治疗中的潜在治疗应用。
Previous studies have attached more importance to growth factors in treating cartilage degeneration and osteoarthritis (OA). Here, the capability of mechano growth factor‐C24E (MGF) to prevent osteoarthritic cartilage degeneration was evaluated in vitro and in vivo. Using in vitro cultured human OA chondrocytes treated with 10–60‐ng/ml MGF for 12 hr, we detected the cell proliferation, migration, and anabolism of OA chondrocytes. The unfolded protein response and the protein characteristic of OA pathology, such as transforming growth factor β, SMAD family member 3, and hypoxia‐inducible factor 2α of OA chondrocytes, were also detected by western blotting. Furthermore, protein kinase RNA‐like endoplasmic reticulum kinase was knocked down via small interfering RNA to illuminate the potential mechanism of MGF's treatment of OA. In a rabbit knee joint OA model, cartilage degeneration was inhibited after 2 weeks of treatment with 0.1–10‐μg/ml MGF. This study demonstrated that MGF treatment can inhibit the pathological apoptosis of OA chondrocytes and promote the proliferation, migration, and matrix synthesis of the chondrocytes. The results also demonstrate that the degeneration of OA cartilage can be delayed by MGF treatment partially via unfolded protein response regulated by protein kinase RNA‐like endoplasmic reticulum kinase and suggest a potential therapeutic application of MGF for OA treatment.