Mirza Eraj Humayun, Pan-Pan Chong, Wan Ibrahim Wan Mohd Azhar Bin, Djordjevic Ivan, Pingguan-Murphy Belinda
Faculty of Engineering, Department of Biomedical Engineering, University of Malaya, Kuala Lumpur, 50603, Kuala Lumpur, Malaysia.
Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
J Biomed Mater Res A. 2015 Nov;103(11):3554-63. doi: 10.1002/jbm.a.35495. Epub 2015 May 27.
Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2 ) and hypoxia (5% O2 ). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture. Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic environment.
关节软骨是一种特别适应低氧张力（缺氧）特定微环境的组织，而这种条件的存在是调节软骨细胞生长和存活的关键因素。锌缺乏与软骨相关疾病有关，并且已知锌的存在具有抗菌益处，这使得在体外系统中加入锌以减少感染具有吸引力。在缺氧条件下培养的聚辛二醇柠檬酸酯（POC）聚合物中加入1%的氧化锌纳米颗粒（ZnONP）的效果尚未得到充分确定。在本研究中，我们研究了ZnONP对在常氧（21% O2）和缺氧（5% O2）条件下培养的软骨细胞增殖和基质合成的影响。我们报告了在缺氧培养中软骨细胞增殖和硫酸化糖胺聚糖（S-GAG）的上调。结果表明，氧浓度和1% ZnONP在合成代谢基因表达（II型胶原蛋白和聚集蛋白聚糖）上调以及分解代谢（MMP-13）基因表达下调方面具有协同作用。此外，在缺氧条件下响应缺氧调节软骨细胞存活的转录因子缺氧诱导因子1A（HIF-1A）的产生不受1% ZnONP存在的影响。1% ZnONP的存在似乎起到了在缺氧环境中维持软骨稳态的作用。
