Altered Lumbar Spine Structure, Biochemistry, and Biomechanical Properties in a Canine Model of Mucopolysaccharidosis Type VII

ABSTRACT: Mucopolysaccharidosis VII (MPSVII) is a lysosomal storage disorder characterized by a deficiency in b-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 inMPSVII, and spine segment and tissue-level mechanical properties, using a naturally occurring caninemodel with a similar clinical phenotype to the human form of the disorder. Segments from juvenileMPSVII 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 elevatedGAG stainingwas 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 highwater content in all regions except the nucleus pulposus.MPSVII spine segments had higher range ofmotion and lower stiffness than controls. Endplate indentation stiffness and failure loadswere significantly lower inMPSVII 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 th