Department of Biomedical and Dental Sciences and Morphofunctional Images, Policlinico Universitario, University of Messina, 98125, Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Torre Biologica, 5° piano, Via C. Valeria, 98125, Messina, Italy.
Inflamm Res. 2018 Jan;67(1):5-20. doi: 10.1007/s00011-017-1084-9. Epub 2017 Aug 12.
Our knowledge of extracellular matrix (ECM) structure and function has increased enormously over the last decade or so. There is evidence demonstrating that ECM provides signals affecting cell adhesion, shape, migration, proliferation, survival, and differentiation. ECM presents many domains that become active after proteolytic cleavage. These active ECM fragments are called matrikines which play different roles; in particular, they may act as potent inflammatory mediators during cartilage injury.
A major component of the ECM that undergoes dynamic regulation during cartilage damage and inflammation is the non-sulphated glycosaminoglycan (GAG) hyaluronan (HA). In this contest, HA is the most studied because of its different activity due to the different polymerization state. In vivo evidences have shown that low molecular weight HA exerts pro-inflammatory action, while high molecular weight HA possesses anti-inflammatory properties. Therefore, the beneficial HA effects on arthritis are not only limited to its viscosity and lubricant action on the joints, but it is especially due to a specific and effective anti-inflammatory activity. Several in vitro experimental investigations demonstrated that HA treatment may regulate different biochemical pathways involved during the cartilage damage. Emerging reports are suggesting that the ability to recognize receptors both for the HA degraded fragments, whether for the high-polymerized native HA involve interaction with integrins, toll-like receptors (TLRs), and the cluster determinant (CD44). The activation of these receptors induced by small HA fragments, via the nuclear factor kappa-light-chain enhancer of activated B cell (NF-kB) mediation, directly or other different pathways, produces the transcription of a large number of damaging intermediates that lead to cartilage erosion.
This review briefly summarizes a number of findings of the recent studies focused on the protective effects of HA, at the different polymerization states, on experimental arthritis in vitro both in animal and human cultured chondrocytes.
在过去的十年左右，我们对细胞外基质（ECM）结构和功能的了解大大增加。有证据表明，ECM 提供了影响细胞黏附、形状、迁移、增殖、存活和分化的信号。ECM 呈现出许多在蛋白水解切割后变得活跃的结构域。这些活性 ECM 片段被称为基质细胞因子，它们发挥不同的作用；特别是，它们在软骨损伤时可能作为有效的炎症介质。
在软骨损伤和炎症过程中，细胞外基质中经历动态调节的主要成分是非硫酸化糖胺聚糖（GAG）透明质酸（HA）。在这种情况下，HA 是研究最多的，因为其不同的聚合状态导致其具有不同的活性。体内证据表明，低分子量 HA 发挥促炎作用，而高分子量 HA 具有抗炎特性。因此，HA 对关节炎的有益作用不仅限于其对关节的粘度和润滑作用，还特别由于其具有特定而有效的抗炎活性。几项体外实验研究表明，HA 处理可能调节软骨损伤过程中涉及的不同生化途径。新出现的报告表明，识别 HA 降解片段的受体的能力，无论是对高聚合天然 HA 的受体，都涉及与整合素、 toll 样受体（TLRs）和簇决定簇（CD44）的相互作用。通过核因子 kappa-轻链增强子活化 B 细胞（NF-kB）介导，小分子 HA 片段激活这些受体，直接或通过其他不同途径，产生大量导致软骨侵蚀的损伤中间体的转录。
本综述简要总结了一些最近的研究结果，这些研究集中在不同聚合状态的 HA 在动物和人培养的软骨细胞体外实验性关节炎中的保护作用。
