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Anti-oxidant and immune-modulatory properties of sulfated alginate derivatives on human chondrocytes and macrophages†
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-06-16 00:00:00 , DOI: 10.1039/c7bm00341b Anne Kerschenmeyer 1, 2, 3, 4, 5 , Øystein Arlov 6, 7, 8, 9 , Vera Malheiro 5, 10, 11, 12, 13 , Matthias Steinwachs 5, 14, 15, 16 , Markus Rottmar 5, 10, 11, 12, 13 , Katharina Maniura-Weber 5, 10, 11, 12, 13 , Gemma Palazzolo 1, 2, 3, 4, 5 , Marcy Zenobi-Wong 1, 2, 3, 4, 5
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-06-16 00:00:00 , DOI: 10.1039/c7bm00341b Anne Kerschenmeyer 1, 2, 3, 4, 5 , Øystein Arlov 6, 7, 8, 9 , Vera Malheiro 5, 10, 11, 12, 13 , Matthias Steinwachs 5, 14, 15, 16 , Markus Rottmar 5, 10, 11, 12, 13 , Katharina Maniura-Weber 5, 10, 11, 12, 13 , Gemma Palazzolo 1, 2, 3, 4, 5 , Marcy Zenobi-Wong 1, 2, 3, 4, 5
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Degeneration of articular cartilage represents one of the most common causes of pain and disability in our aging society. Current treatments only address the symptoms of joint disease, but not their underlying causes which include oxidative stress and inflammation in cartilage and surrounding tissues. Sulfated biopolymers that mimic aspects of the native extracellular environment of cartilage are recently gaining interest as a means to slow the inflammatory events responsible for tissue degeneration. Here we show that the natural polysaccharide alginate and particularly its sulfated derivatives have potent anti-oxidant, anti-inflammatory and anti-immunogenic properties in vitro. We found that these polymers exert a free radical scavenging activity in a sulfation-dependent manner. In particular, the sulfation degree of substitution of alginate directly correlated with its ability to scavenge superoxide radicals and to chelate metal ions. We also studied the effect of sulfated alginate on the ability of IL-1β to stimulate inflammatory genes in human chondrocytes and found decreased expression of the pro-inflammatory markers IL-6 and CXCL8, which inversely correlated with the sulfation degree. Moreover, in studies testing the ability of the alginates to modulate macrophage polarization, we found that they decreased both the gene expression and synthesis of the proinflammatory cytokine TNF-α in human THP-1 macrophages with M1-like phenotype in a sulfation-dependent manner. To conclude, sulfated alginates effectively protect against oxidative stress and inflammation in vitro and are a promising biomaterial to be explored for treatment of osteoarthritis.
中文翻译：
硫酸藻酸盐衍生物对人软骨细胞和巨噬细胞的抗氧化和免疫调节作用†
关节软骨变性是我们衰老社会中最常见的疼痛和残疾原因之一。当前的治疗仅针对关节疾病的症状，而不针对其根本原因，包括氧化应激和软骨及周围组织的炎症。模仿软骨天然细胞外环境方面的硫酸化生物聚合物作为一种减缓引起组织变性的炎症事件的手段而引起了人们的关注。在这里，我们显示了天然多糖藻酸盐，特别是其硫酸盐衍生物在体外具有有效的抗氧化，抗炎和抗免疫原性的特性。我们发现这些聚合物以硫酸盐依赖性方式发挥自由基清除活性。特别地，藻酸盐的硫酸化取代度与其清除超氧自由基和螯合金属离子的能力直接相关。我们还研究了硫酸化藻酸盐对IL-1β刺激人软骨细胞中炎性基因能力的影响，并发现促炎性标志物IL-6和CXCL8的表达降低，它与硫酸化度成反比。此外，在测试藻酸盐调节巨噬细胞极化能力的研究中，我们发现它们以硫酸盐依赖性方式降低了具有M1样表型的人THP-1巨噬细胞中促炎细胞因子TNF-α的基因表达和合成。 。总而言之，硫酸盐藻酸盐在体外能有效地抵抗氧化应激和炎症，是一种有望用于治疗骨关节炎的生物材料。
更新日期：2017-06-16
中文翻译：
硫酸藻酸盐衍生物对人软骨细胞和巨噬细胞的抗氧化和免疫调节作用†
关节软骨变性是我们衰老社会中最常见的疼痛和残疾原因之一。当前的治疗仅针对关节疾病的症状，而不针对其根本原因，包括氧化应激和软骨及周围组织的炎症。模仿软骨天然细胞外环境方面的硫酸化生物聚合物作为一种减缓引起组织变性的炎症事件的手段而引起了人们的关注。在这里，我们显示了天然多糖藻酸盐，特别是其硫酸盐衍生物在体外具有有效的抗氧化，抗炎和抗免疫原性的特性。我们发现这些聚合物以硫酸盐依赖性方式发挥自由基清除活性。特别地，藻酸盐的硫酸化取代度与其清除超氧自由基和螯合金属离子的能力直接相关。我们还研究了硫酸化藻酸盐对IL-1β刺激人软骨细胞中炎性基因能力的影响，并发现促炎性标志物IL-6和CXCL8的表达降低，它与硫酸化度成反比。此外，在测试藻酸盐调节巨噬细胞极化能力的研究中，我们发现它们以硫酸盐依赖性方式降低了具有M1样表型的人THP-1巨噬细胞中促炎细胞因子TNF-α的基因表达和合成。 。总而言之，硫酸盐藻酸盐在体外能有效地抵抗氧化应激和炎症，是一种有望用于治疗骨关节炎的生物材料。
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