111 Project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, China.
Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
J Tissue Eng Regen Med. 2018 Mar;12(3):738-749. doi: 10.1002/term.2493. Epub 2017 Oct 6.
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.
先前的研究更注重生长因子在治疗软骨退变和骨关节炎（OA）中的作用。在这里，我们评估了机械生长因子-C24E（MGF）在体外和体内预防骨关节炎软骨退变的能力。我们使用体外培养的人 OA 软骨细胞，用 10-60-ng/ml 的 MGF 处理 12 小时，检测 OA 软骨细胞的增殖、迁移和合成代谢。通过 Western blot 检测 OA 软骨细胞未折叠蛋白反应和 OA 病理特征的蛋白质，如转化生长因子 β、SMAD 家族成员 3 和缺氧诱导因子 2α。此外，通过小干扰 RNA 敲低蛋白激酶 RNA 样内质网激酶，阐明 MGF 治疗 OA 的潜在机制。在兔膝关节 OA 模型中，用 0.1-10-μg/ml 的 MGF 治疗 2 周后，软骨退变得到抑制。本研究表明，MGF 治疗可抑制 OA 软骨细胞的病理性凋亡，并促进软骨细胞的增殖、迁移和基质合成。结果还表明，MGF 治疗通过蛋白激酶 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 治疗 OA 的潜在治疗应用。
