Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907.
Macromol Biosci. 2013 Sep;13(9):1228-37. doi: 10.1002/mabi.201300112. Epub 2013 Jul 8.
Aggrecan, a major macromolecule in cartilage, protects the extracellular matrix (ECM) from degradation during the progression of osteoarthritis (OA). However, aggrecan itself is also susceptible to proteolytic cleavage. Here, the use of a biomimetic proteoglycan (mAGC) is presented, which functionally mimics aggrecan but lacks the known cleavage sites, protecting the molecule from proteolytic degradation. The objective of this study is to test the efficacy of this molecule in ex vivo (human OA synovial fluid) and in vivo (Sprague-Dawley rats) osteoarthritic models. These results indicate that mAGC's may protect articular cartilage against the loss of key ECM components, and lower catabolic protein and gene expression in both models. This suppression of matrix degradation has the potential to provide a healthy environment for tissue repair.
聚集蛋白聚糖(aggrecan)是软骨中的主要大分子物质,可在骨关节炎(OA)进展过程中保护细胞外基质(ECM)免受降解。然而,聚集蛋白聚糖本身也容易受到蛋白水解的影响。在这里,提出了使用仿生蛋白聚糖(mAGC),它在功能上模拟聚集蛋白聚糖,但缺乏已知的切割位点,从而保护分子免受蛋白水解降解。本研究的目的是测试该分子在体外(人 OA 滑液)和体内(斯普拉格-道利大鼠)骨关节炎模型中的功效。这些结果表明,mAGC 可能保护关节软骨免受关键 ECM 成分的丢失,并降低两种模型中蛋白和基因的表达。基质降解的抑制有可能为组织修复提供健康的环境。