Molecular Basis of Anti-Inflammatory Action of Platelet-Rich Plasma on Human Chondrocytes: Mechanisms of NF-κB Inhibition Via HGF
Molecular Basis of Anti-Inflammatory Action of Platelet-Rich Plasma on Human Chondrocytes: Mechanisms of NF-κB Inhibition Via HGF
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DOI：
10.1002/jcp.22274
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发表时间：
2010-12-01
影响因子：
5.6
通讯作者：
Desiderio, Maria Alfonsina
中科院分区：
文献类型：
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作者：
Bendinelli, Paola;Matteucci, Emanuela;Desiderio, Maria Alfonsina
由于损伤或疾病而导致的关节软骨损失带来了重大的临床挑战，这也是因为软骨的再生能力非常差，从而促进了生物学方法的发展。作为自体血液产品，富含血小板的血浆（PRP）通过促进安全和自然的愈合，提供了一种有前途的手术替代方案。在这里，我们测试了 PRP 作为一种有效抗炎剂的可能性，为关节软骨的再生提供了有吸引力的基础，并进行了两项主要观察。首先，软骨细胞中激活的 PRP 降低了炎症过程关键调节因子 NF-κ B 的反式激活活性，并降低了 COX-2 和 CXCR4 靶基因的表达。通过分析一组具有不同生物学意义的细胞因子，我们观察到活化的 PRP 中肝细胞生长因子 (HGF)、白细胞介素 4 和肿瘤坏死因子-α (TNF-α) 的增加。 HGF 和 TNF-α 通过破坏 NF-κ B 反式激活活性，对于激活的 PRP 的抗炎功能非常重要。 PRP 对 NF-κ B 活性的抑制作用涉及的关键分子机制是，对于 HGF 而言，细胞 IkB α 表达增强，这有助于 NF-κ B-p65 亚基保留在细胞质中并进行核质穿梭；对于 TNF-α 来说，p50/50 DNA 结合导致靶基因表达受到抑制。其次，U937单核细胞中激活的PRP通过抑制趋化因子反式激活和CXCR4受体表达来减少趋化性，从而可能控制软骨的局部炎症。总之，活化的PRP是一种有前途的生物治疗剂，作为微创关节软骨再生的支架，不仅因为其增殖/分化生长因子的含量，而且还因为存在包括HGF在内的抗炎剂。 J.细胞。生理学。 225：757-766，2010。 (C) 2010 Wiley-Liss, Inc.
Loss of articular cartilage through injury or disease presents major clinical challenges also because cartilage has very poor regenerative capacity, giving rise to the development of biological approaches. As autologous blood product, platelet-rich plasma (PRP) provides a promising alternative to surgery by promoting safe and natural healing. Here we tested the possibility that PRP might be effective as an anti-inflammatory agent, providing an attractive basis for regeneration of articular cartilage, and two principal observations were done. First, activated PRP in chondrocytes reduced the :transactivating activity of NF-kappa B, critical regulator of the inflammatory process, and decreased the expression of COX-2 and CXCR4 target genes. By analyzing a panel of cytokines with different biological significance, in activated PRP we observed increases in hepatocyte growth factor (HGF), interleukin-4 and tumor necrosis factor-alpha (TNF-alpha). HGF and TNF-alpha, by disrupting NF-kappa B-transactivating activity, were important for the anti-inflammatory function of activated PRP. The key molecular mechanisms involved in PRP-inhibitory effects on NF-kappa B activity were for HGF the enhanced cellular IkB alpha expression, that contributed to NF-kappa B-p65 subunit retention in the cytosol and nucleo-cytoplasmic shuttling, and for TNF-alpha the p50/50 DNA-binding causing inhibition of target-gene expression. Second, activated PRP in U937-monocytic cells reduced chemotaxis by inhibiting chemokine transactivation and CXCR4-receptor expression, thus possibly controlling local inflammation in cartilage. In conclusion, activated PRP is a promising biological therapeutic agent, as a scaffold in micro-invasive articular cartilage regeneration, not only for its content of proliferative/differentiative growth factors, but also for the presence of anti-inflammatory agents including HGF. J. Cell. Physiol. 225: 757-766,2010. (C) 2010 Wiley-Liss, Inc.