Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil; Department of Biosciences, Universidade Federal de São Paulo, Santos, São Paulo, Brazil.
Acta Histochem. 2021 Feb;123(2):151678. doi: 10.1016/j.acthis.2020.151678. Epub 2021 Jan 9.
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by alpha-L-iduronidase (IDUA) deficiency, an enzyme responsible for glycosaminoglycan degradation. Musculoskeletal impairment is an important component of the morbidity related to the disease, as it has a major impact on patients' quality of life. To understand how this disease affects bone structure, morphological, biomechanical and histological analyses of femurs from 3- and 6-month-old wild type (Idua +/+) and MPS I knockout mice (Idua -/-) were performed. Femurs from 3-month-old Idua -/- mice were found to be smaller and less resistant to fracture when compared to their age matched controls. In addition, at this age, the femurs presented important alterations in articular cartilage, trabecular bone architecture, and deposition of type I and III collagen. At 6 months of age, femurs from Idua -/- mice were more resistant to fracture than those from Idua +/+. Our results suggest that the abnormalities observed in bone matrix and articular cartilage in 3-month-old Idua -/- animals caused bone tissue to be less flexible and more likely to fracture, whereas in 6-month-old Idua -/- group the ability to withstand more load before fracturing than wild type animals is possibly due to changes in the bone matrix.
黏多糖贮积症 I 型(MPS I)是一种溶酶体贮积症,其特征为α-L-艾杜糖苷酸酶(IDUA)缺乏,该酶负责糖胺聚糖的降解。肌肉骨骼损伤是与该疾病相关的发病率的一个重要组成部分,因为它对患者的生活质量有重大影响。为了了解这种疾病如何影响骨骼结构,对 3 个月和 6 个月大的野生型(Idua +/+)和 MPS I 基因敲除小鼠(Idua -/-)的股骨进行了形态学、生物力学和组织学分析。与年龄匹配的对照组相比,3 个月大的 Idua -/- 小鼠的股骨更小,更易骨折。此外,在这个年龄段,关节软骨、小梁骨结构以及 I 型和 III 型胶原的沉积都出现了重要的改变。在 6 个月大时,Idua -/- 小鼠的股骨比 Idua +/+ 小鼠更能抵抗骨折。我们的结果表明,3 个月大的 Idua -/- 动物的骨基质和关节软骨中观察到的异常导致骨组织的柔韧性降低,更容易骨折,而在 6 个月大的 Idua -/- 组中,比野生型动物更能承受更大的负荷而不骨折,可能是由于骨基质的改变。