Université Paris Cité, Institut des maladies musculo-squelettiques, Laboratory Orofacial Pathologies, Imaging and Biotherapies URP2496 and FHU-DDS-Net, Dental School, and Plateforme d'Imagerie du Vivant (PIV), Montrouge, France; Department of Rheumatology, Cochin Hospital, Université Paris Cité, Paris, France.
Université Paris Cité, Institut des maladies musculo-squelettiques, Laboratory Orofacial Pathologies, Imaging and Biotherapies URP2496 and FHU-DDS-Net, Dental School, and Plateforme d'Imagerie du Vivant (PIV), Montrouge, France; Centre de référence des maladies rares du métabolisme du calcium et du phosphate, Plateforme d'expertise maladies rares Paris Saclay, filière OSCAR, EndoRare and BOND ERN, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Bone. 2024 Jan;178:116931. doi: 10.1016/j.bone.2023.116931. Epub 2023 Oct 13.
Bone disorders may affect the skeleton in different ways, some bones being very impaired and others less severely. In translational studies using murine models of human skeletal diseases, the bone phenotype is mainly evaluated at the distal femur or proximal tibia. The sacroiliac joint (SIJ), which connects the spine to the pelvis, is involved in the balanced transfer of mechanical energy from the lumbar spine to the lower extremities. Because of its role in biomechanical stress, the SIJ is a region of particular interest in various bone diseases. Here we aimed to characterize the SIJ in several murine models to develop a highly reliable tool for studying skeletal disorders. We performed a 12-month in vivo micro-computed tomography (micro-CT) follow-up to characterize the SIJ in wild-type (WT) C57BL/J6 mice and compared the bone microarchitecture of the SIJ and the distal femur at 3 months by micro-CT and histology. To test the sensitivity of our methodology, the SIJ and distal femur were evaluated at 3 and 6 months, in 2 murine models of skeletal disorder, X-linked hypophosphatemia (Hyp mice) and HLA-B27 transgenic mice and compared to WT mice. A multimodal analysis was performed, using a combination of microCT and histological analysis. With the Hyp model, the SIJ displayed more bone microarchitecture alterations than the distal femur. Hyp mice showed a significant reduction in trabecular bone at both the distal femur and sacral slope as compared with WT mice, with a significant positive correlation between trabecular bone parameters of the distal femur and sacral side of the SIJ. Furthermore, trabecular bone parameters (Bone Volume/Total Volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), trabecular pattern factor (Tb.Pf)) were significantly increased compared to femoral parameters at the SIJ. The sacral articular cortical bone, which is indicative of osteoarticular lesions, was altered in Hyp mice. Interestingly, in accordance to previous studies, HLA-B27 transgenic mice did not show any osteoarticular lesions as compared with WT mice. Cortical bone parameters (thickness, porosity), as well as scoring performed with double blinding, did not show difference between the 2 genotypes. The characterization and evaluation of the SIJ surface appears very sensitive to emphasize alterations of bone and joint. The SIJ may represent a valuable tool to investigate both bone and local osteoarticular alterations in murine models of skeletal disorders and might be a relevant site for assessing the response to treatment of chronic bone diseases.
骨骼疾病可能以不同的方式影响骨骼，有些骨骼受到严重影响，而有些则影响较小。在使用人类骨骼疾病的鼠模型进行转化研究时，主要在远端股骨或近端胫骨评估骨骼表型。骶髂关节 (SIJ) 将脊柱连接到骨盆，它在将腰椎的机械能量平衡传递到下肢中起着重要作用。由于其在生物力学应力中的作用，SIJ 是各种骨骼疾病中特别感兴趣的区域。在这里，我们旨在对几种鼠模型中的 SIJ 进行特征描述，以开发一种用于研究骨骼疾病的高度可靠工具。我们进行了为期 12 个月的体内 micro-CT (micro-CT) 随访，以对 WT C57BL/J6 小鼠的 SIJ 进行特征描述，并通过 micro-CT 和组织学比较 3 个月时 SIJ 和远端股骨的骨微结构。为了测试我们方法的敏感性，在 2 种骨骼疾病模型（X 连锁低磷血症 (Hyp) 小鼠和 HLA-B27 转基因小鼠）中，在 3 个月和 6 个月时评估了 SIJ 和远端股骨，并与 WT 小鼠进行了比较。使用 microCT 和组织学分析的组合进行了多模态分析。与 Hyp 模型相比，SIJ 显示出更多的骨微结构改变。与 WT 小鼠相比，Hyp 小鼠的远端股骨和骶骨斜率的小梁骨均明显减少，远端股骨和 SIJ 骶骨侧的小梁骨参数之间存在显著的正相关。此外，与股骨参数相比，小梁骨参数（骨体积/总体积 (BV/TV)、小梁厚度 (Tb.Th)、小梁间隔 (Tb.Sp)、小梁数量 (Tb.N)、小梁图案因子 (Tb.Pf)) 在 SIJ 处显著增加。表明骨关节炎病变的骶骨关节皮质骨在 Hyp 小鼠中发生改变。有趣的是，与之前的研究一致，与 WT 小鼠相比，HLA-B27 转基因小鼠没有任何骨关节炎病变。皮质骨参数（厚度、孔隙率）以及双盲评分均未显示两种基因型之间的差异。SIJ 表面的特征描述和评估似乎非常敏感，可以强调骨骼和关节的变化。SIJ 可能是研究骨骼疾病鼠模型中骨骼和局部骨关节炎变化的有价值工具，并且可能是评估慢性骨骼疾病治疗反应的相关部位。
