De Franceschi L, Roseti L, Desando G, Facchini A, Grigolo B
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
Osteoarthritis Cartilage. 2007 Nov;15(11):1311-7. doi: 10.1016/j.joca.2007.04.008. Epub 2007 Jun 4.
To investigate the gene expression profile and the histological aspects of articular cartilage of patients affected by Morquio syndrome, a lysosomal storage disease characterized by the accumulation of glycosaminoglycans within the cells which result in abnormal formation and growth of the skeletal system.
Articular cartilage samples were obtained from the femoral condyle of two siblings with Morquio syndrome during surgery performed to treat valgus knee. As controls, four biopsy samples of healthy cartilage were obtained from four different male multiorgan donors. A Real-Time Polymerase Chain reaction (RT-PCR) analysis was performed to evaluate the expression of type I and II collagens and aggrecan mRNAs. Histological and immunohistochemical analyses for some matrix proteins were carried out on paraffin embedded sections.
Type I collagen mRNA mean level was higher in the samples of patients with Morquio syndrome compared to controls. Type II collagen and aggrecan mRNAs' mean expression was instead lower. The morphological appearance of the cartilage showed a poorly organized tissue structure with not homogeneously distributed cells that were larger compared to normal chondrocytes due to the presence inside the vacuoles of proteoglycans which were not metabolized. Chondrocytes were negative for collagen II immunostaining while the extracellular matrix was weakly positive. Collagen type I immunostaining was positive at cellular level. Keratan sulfate showed diffuse positivity and chondroitin-6-sulfate was present throughout the cartilaginous thickness.
In cartilage of patients with Morquio syndrome, a low expression of collagen type II and a high expression of collagen type I both at protein and molecular levels are evidentiated. This finding could give evidence of the reduction in ankle and knee joint movement observable in these patients.
研究黏多糖贮积症Ⅳ型（Morquio综合征）患者关节软骨的基因表达谱及组织学特征。Morquio综合征是一种溶酶体贮积病，其特征是细胞内糖胺聚糖蓄积，导致骨骼系统异常形成和生长。
在治疗膝外翻的手术中，从两名患有Morquio综合征的兄弟姐妹的股骨髁获取关节软骨样本。作为对照，从四名不同的男性多器官供体获取四个健康软骨活检样本。进行实时聚合酶链反应（RT-PCR）分析以评估Ⅰ型和Ⅱ型胶原蛋白以及聚集蛋白聚糖mRNA的表达。对石蜡包埋切片进行一些基质蛋白的组织学和免疫组织化学分析。
与对照组相比，Morquio综合征患者样本中Ⅰ型胶原蛋白mRNA的平均水平更高。相反，Ⅱ型胶原蛋白和聚集蛋白聚糖mRNA的平均表达更低。软骨的形态外观显示组织结构紊乱，细胞分布不均匀，由于未代谢的蛋白聚糖存在于液泡中，这些细胞比正常软骨细胞更大。软骨细胞Ⅱ型胶原蛋白免疫染色呈阴性，而细胞外基质呈弱阳性。Ⅰ型胶原蛋白免疫染色在细胞水平呈阳性。硫酸角质素呈弥漫性阳性，硫酸软骨素-6在整个软骨厚度中均有存在。
在Morquio综合征患者的软骨中，在蛋白质和分子水平上均明显表现出Ⅱ型胶原蛋白低表达和Ⅰ型胶原蛋白高表达。这一发现可能为这些患者中观察到的踝关节和膝关节活动减少提供证据。
