A tree shrew model for steroid-associated osteonecrosis
摘要: 骨坏死是骨科常见的人类疾病。治疗困难，半数患者可能需要人工关节置换，造成较大的经济负担，导致生活质量下降。激素是造成骨坏死的主要原因之一，高剂量的皮质类固醇被认为是造成骨坏死最危险的因素。由于该病治疗的复杂性，我们需要更好的动物模型，可以广泛用于药物开发和测试等。树鼩与灵长类动物的关系比啮齿类动物和灵长类动物的关系更密切。我们成功建立了一个树鼩模型来建立和评估类固醇相关性骨坏死(SAON)。联合使用低剂量脂多糖(LPS)和高剂量甲基强的松龙(MPS)，12周后可建立骨坏死树鼩模型。血清生化和组织病理学分析表明，该树鼩模型是理想的。因此，这项工作为类固醇相关性骨坏死的研究和治疗方法的优化提供了一个有用的动物模型。Abstract: Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.
- Steroid-associated osteonecrosis /
- Tree shrews /
- Biochemical parameter analysis /
- Micro-CT examination /
- Histological analysis /
- Scanning electronmicroscope observation
Figure 1. Micro-CT analysis, histological evaluation, and SEM analysis of femoral heads in control and SAON groups
A: In control group, femoral heads were properly shaped, with no evidence of cortical bone collapse, and trabecular bone was uniform, dense, continuous, and of normal thickness. In SAON group, femoral heads showed changes in shape, with evidence of cortical bone partial collapse, trabecular fracture, trabecular sparseness, thinning, and increased intercellular spacing. B: Micro-CT evaluation of control and SAON groups. All data are presented as mean±SD (n=6). *: P<0.05, **: P<0.01, vs. control group. BMD: Bone mineral density; BV/TV: Bone tissue volume fraction; BS/BV: Bone surface/volume ratio; Tb. N: Trabecular number; Tb. Th: Trabecular thickness; Tb. Sp: Trabecular separation. C, D: In control group, bone trabeculae were dense and intact, rich in bone marrow cells, and contained only a few fused adipose cells. In SAON group, trabecular bone displayed a disordered structure that appeared thinner and sparser, showed partial fractures, and contained adipose cells that were fused into vacuoles; bone trabeculae in SAON group contained more empty lacunae when compared to those in control group. E, F: In control group, bone trabeculae were dense, trabecular spacing was small (at low magnification), trabecular surface was smooth, and there were dense bone fibers (at high magnification). G–J: In SAON group, bone trabeculae were sparser, trabecular spacing was increased (at low magnification), and trabecular bone surface was disordered (at high magnification).
Table 1. Micro-CT evaluation of control and SAON groups (n=6, X±S)
Group BMD value BV/TV (%) BS/BV (/mm) Tb. Th (mm) Tb. Sp (mm) Tb. N (/mm) Control 0.5410±0.0333 45.43±3.87 28.72±4.69 0.11±0.01 0.21±0.01 4.28±0.22 SAON 0.4709±0.0492＊ 38.03±5.05＊ 32.11±5.53△ 0.10±0.02△ 0.25±0.02＊＊ 3.77±0.27＊＊ BMD: Bone mineral density; BV/TV: Bone tissue volume fraction; BS/BV: Bone surface/volume ratio; Tb. Th: Trabecular thickness; Tb. Sp: Trabecular separation; Tb. N: Trabecular number. Compared with control group, △: P>0.05, ＊: P<0.05, ＊＊: P<0.01.
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