Programa de pós-graduação em medicina: ciências medicas, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
Int J Exp Pathol. 2013 Oct;94(5):305-11. doi: 10.1111/iep.12033. Epub 2013 Jun 21.
Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterized by mutations in enzymes that degrade glycosaminoglycans (GAGs). Joint disease is present in most forms of MPS, including MPS I. This work aimed to describe the joint disease progression in the murine model of MPS I. Normal (wild-type) and MPS I mice were sacrificed at different time points (from 2 to 12 months). The knee joints were collected, and haematoxylin-eosin staining was used to evaluate the articular architecture. Safranin-O and Sirius Red staining was used to analyse the proteoglycan and collagen content. Additionally, we analysed the expression of the matrix-degrading metalloproteinases (MMPs), MMP-2 and MMP-9, using immunohistochemistry. We observed progressive joint alterations from 6 months, including the presence of synovial inflammatory infiltrate, the destruction and thickening of the cartilage extracellular matrix, as well as proteoglycan and collagen depletion. Furthermore, we observed an increase in the expression of MMP-2 and MMP-9, which could conceivably explain the degenerative changes. Our results suggest that the joint disease in MPS I mice may be caused by a degenerative process due to increase in proteases expression, leading to loss of collagen and proteoglycans. These results may guide the development of ancillary therapies for joint disease in MPS I.
黏多糖贮积症（MPS）是一种溶酶体贮积病，其特征是降解糖胺聚糖（GAG）的酶发生突变。大多数 MPS 形式都存在关节疾病，包括 MPS I。本研究旨在描述 MPS I 小鼠模型中的关节疾病进展。正常（野生型）和 MPS I 小鼠在不同时间点（从 2 个月到 12 个月）被处死。收集膝关节，进行苏木精-伊红染色以评估关节结构。番红 O 和天狼星红染色用于分析蛋白聚糖和胶原含量。此外，我们使用免疫组织化学分析基质降解金属蛋白酶（MMPs），MMP-2 和 MMP-9 的表达。我们观察到从 6 个月开始关节逐渐发生改变，包括滑膜炎症浸润、软骨细胞外基质的破坏和增厚，以及蛋白聚糖和胶原的耗竭。此外，我们观察到 MMP-2 和 MMP-9 的表达增加，这可能可以解释退行性变化。我们的结果表明，MPS I 小鼠的关节疾病可能是由于蛋白酶表达增加导致的退行性过程引起的，从而导致胶原和蛋白聚糖的丧失。这些结果可能为 MPS I 中的关节疾病的辅助治疗提供指导。
