Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, leading to accumulation of incompletely degraded heparan, dermatan and chondroitin sulfate glycosaminoglycans. Patients with MPS VII exhibit progressive spinal deformity, which decreases quality of life. Previously, we demonstrated that MPS VII dogs exhibit impaired initiation of secondary ossification in the vertebrae and long bones. The objective of this study was to build on these findings and comprehensively characterize how vertebral bone disease manifests progressively in MPS VII dogs throughout postnatal growth. Vertebrae were collected postmortem from MPS VII and healthy control dogs at seven ages ranging from 9 to 365 days. Microcomputed tomography and histology were used to characterize bone properties in primary and secondary ossification centers. Serum was analyzed for bone turnover biomarkers. Results demonstrated that not only was secondary ossification delayed in MPS VII vertebrae, but that it progressed aberrantly and was markedly diminished even at 365 days-of-age. Within primary ossification centers, bone volume fraction and bone mineral density were significantly lower in MPS VII at 180 and 365 days-of-age. MPS VII growth plates exhibited significantly lower proliferative and hypertrophic zone cellularity at 90 days-of-age, while serum bone-specific alkaline phosphatase (BAP) was significantly lower in MPS VII dogs at 180 days-of-age. Overall, these findings establish that vertebral bone formation is significantly diminished in MPS VII dogs in both primary and secondary ossification centers during postnatal growth.

粘多糖贮积症 (MPS) VII 是一种溶酶体贮积症，其特征是 β-葡萄糖醛酸酶活性不足，导致不完全降解的乙酰肝素、皮肤素和硫酸软骨素糖胺聚糖的积累。MPS VII 患者表现出进行性脊柱畸形，这会降低生活质量。以前，我们证明 MPS VII 犬的椎骨和长骨中的继发性骨化开始受损。本研究的目的是建立在这些发现的基础上，并全面描述椎骨疾病如何在 MPS VII 犬的整个产后生长过程中逐渐表现出来。从 MPS VII 和健康对照犬的死后收集椎骨，年龄从 9 天到 365 天不等 7 个。微计算机断层扫描和组织学用于表征初级和次级骨化中心的骨骼特性。分析血清的骨转换生物标志物。结果表明，不仅 MPS VII 椎骨的继发性骨化延迟，而且其进展异常，甚至在 365 日龄时也明显减少。在初级骨化中心内，MPS VII 在 180 日龄和 365 日龄时骨体积分数和骨矿物质密度显着降低。MPS VII 生长板在 90 日龄时表现出显着降低的增殖和肥大区细胞结构，而在 180 日龄时 MPS VII 犬的血清骨特异性碱性磷酸酶 (BAP) 显着降低。全面的，