McKay Orthopaedic Research Laboratory, Department of Orthopedic Surgery, University of Pennsylvania, 424 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.
J Orthop Res. 2010 May;28(5):616-22. doi: 10.1002/jor.21030.
Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disorder characterized by a deficiency in beta-glucuronidase activity, leading to systemic accumulation of poorly degraded glycosaminoglycans (GAG). Along with other morbidities, MPS VII is associated with pediatric spinal deformity. The objective of this study was to examine potential associations between abnormal lumbar spine matrix structure and composition in MPS VII, and spine segment and tissue-level mechanical properties, using a naturally occurring canine model with a similar clinical phenotype to the human form of the disorder. Segments from juvenile MPS VII and unaffected dogs were allocated to: radiography, gross morphology, histology, biochemistry, and mechanical testing. MPS VII spines had radiolucent lesions in the vertebral body epiphyses. Histologically, this corresponded to a GAG-rich cartilaginous region in place of bone and elevated GAG staining was seen in the annulus fibrosus. Biochemically, MPS VII samples had elevated GAG in the outer annulus fibrosus and epiphyses, low calcium in the epiphyses, and high water content in all regions except the nucleus pulposus. MPS VII spine segments had higher range of motion and lower stiffness than controls. Endplate indentation stiffness and failure loads were significantly lower in MPS VII samples, while annulus fibrosus tensile mechanical properties were normal. Vertebral body lesions in MPS VII spines suggest a failure to convert cartilage to bone during development. Low stiffness in these regions likely contributes to mechanical weakness in motion segments and is a potential factor in the progression of spinal deformity.
黏多糖贮积症 VII 型（MPS VII）是一种溶酶体贮积病，其特征是β-葡萄糖醛酸酶活性缺乏，导致未降解的糖胺聚糖（GAG）在全身积累。除其他疾病外，MPS VII 还与儿科脊柱畸形有关。本研究的目的是使用具有与该疾病人类表型相似的临床表型的天然发生的犬模型，研究 MPS VII 中腰椎基质结构和组成与脊柱节段和组织水平机械性能之间的潜在关联。将幼年 MPS VII 和未受影响的犬的节段分配到以下组别：放射学、大体形态学、组织学、生物化学和机械测试。MPS VII 的脊柱在椎体骺上有透光性病变。组织学上，这对应于富含 GAG 的软骨区域代替了骨骼，并且在纤维环中可见 GAG 染色升高。生物化学上，MPS VII 样本的外纤维环和骺上 GAG 含量升高，骺上钙含量降低，除了核髓外，所有区域的水含量均升高。MPS VII 脊柱节段的运动范围较大，刚度较低。MPS VII 样本的终板压痕刚度和失效载荷明显较低，而纤维环的拉伸力学性能正常。MPS VII 脊柱的椎体病变表明在发育过程中软骨未能转化为骨骼。这些区域的低刚度可能导致运动节段的机械强度减弱，是脊柱畸形进展的潜在因素。
