基于ITS探讨软骨下骨rod-plate微结构重塑在骨关节炎发病机制中的作用

The pathogenesis of osteoarthritis (OA) is still unclear, and it has been suggested that subchondral bone microstructure and remodeling plays an important role in it. Studies found that the abnormal subchondral bone resorption precedes OA cartilage changes. However, how subchondral bone resorption contributes to cartilage degradation is largely unknown. Recently, a novel technique, Individual Trabecula Segmentation (ITS), has been developed, which is able to discompose the whole trabecular bone into individual plates and rods and quantify the rod-plate microstructure. Using this technique, we detected the rod-plate microstructure changes of subchondral bone from knee OA patients. We found that in subregions with histologically intact cartilage in the OA group, bone volume fraction of subchondral bone did not change; nevertheless, the rod bone volume fraction and trabecular number were decreased significantly in OA group. Thus, it was hypothesized that trabecular rod loss may lead to uneven distribution of rod-plate microstructure, resulting in increased shear stresses and damage in cartilage. Based on these findings, we plan to further explore the role of subchondral rod-plate microstructure and remodeling in OA pathogenesis in this project. Tibial plateaus from knee OA patients during total knee arthroplasty and the knee joints from guinea pigs with spontaneous OA will be used. Cartilage damage will be estimated by histology, then the changes in rod-plate microstructure and mechanical properties of subchondral bone will be investigated by ITS and finite element analysis, respectively. To explore the mechanism of the changes in rod-plate microstructure and remodeling in subchondral bone, the numbers of preosteoclasts, osteoclasts, osteoprogenitors, osteoblasts and endothelial cells and the expression of related cytokine will be detected. This study will shed new light on the role of subchondral bone rod-plate microstructure and remodeling in OA pathogenesis, and also provide a new strategy for the treatment and early detection of OA in humans.

骨关节炎(OA)发病机制未明，软骨下骨微结构重塑改变与其密切相关。研究发现，OA发病中软骨下骨的异常骨吸收早于软骨改变，但其致病机制未明。单个骨小梁分解(ITS)技术可将骨组织分解为单个杆状(rod)或板状(plate)骨小梁并确定其数目和方向。利用该技术，我们研究发现在OA病人软骨完好区域，虽然软骨下骨总骨量不变，但rod的骨量和数目明显降低。我们推测rod丢失造成rod和plate不均匀分布，进而诱发软骨退变。本项目拟以OA病人标本和豚鼠自发性OA模型为对象，组织学评估软骨退变, ITS和有限元分析检测软骨下骨rod-plate微结构和力学性能变化；免疫染色检测破骨前体/破骨细胞、成骨前体/成骨细胞、血管内皮细胞活性及相关因子表达，以揭示微结构重塑改变的细胞机制。本项目将在单个骨小梁水平阐明软骨下骨rod-plate微结构重塑在OA发病中的作用，为OA治疗和早期诊断提供理论和实验依据。

骨关节炎(OA)发病机制未明，软骨下骨微结构重塑改变与其密切相关。研究发现，OA发病中软骨下骨的异常骨吸收早于软骨改变，但其致病机制未明。单个骨小梁分解(ITS)技术可将骨组织分解为单个杆状(rod)或板状(plate)骨小梁并确定其数目和方向。利用该技术，我们研究发现在OA病人软骨完好区域，虽然软骨下骨总骨量不变，但rod的骨量和数目明显降低。我们推测rod丢失造成rod和plate不均匀分布，进而诱发软骨退变。本项目通过以OA病人标本和豚鼠自发性OA模型为对象，组织学评估软骨退变, ITS和有限元分析软检测骨下骨rod-plate微结构和力学性能变化；免疫染色检测破骨前体/破骨细胞、成骨前体/成骨细胞、血管内皮细胞活性及相关因子表达，揭示了微结构重塑改变的细胞机制。本项目在单个骨小梁水平阐明软骨下骨rod-plate微结构重塑在OA发病中的作用，为OA治疗和早期诊断提供理论和实验依据。

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