Osteoarthritis (OA) is the most common joint disease globally. In OA, articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. Especially, it is technically challenging to identify calcified cartilage, where relevant but poorly understood pathological processes like tidemark multiplication and advancement occur. Here, we used state-of-the art micro-focus small-angle X-ray scattering with high 5μm spatial resolution to determine mineral crystal thickness in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from the medial and lateral compartments of medial compartment knee OA patients (n=15) and cadaver knees (n=10). For the first time, we identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32nm thicker crystals compared to the rest of calcified cartilage. In addition, we found 0.2nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process since the lateral compartment is typically less loaded in medial compartment knee OA. Furthermore, the crystal thickness of the subchondral bone was lower with increasing histopathological OA severity. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee is associated with the growth of mineral crystals, which is especially evident in the calcified cartilage. In the subchondral bone, mineral crystals become thinner with increasing OA severity, which indicates new bone formation with sclerosis.

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健康和骨关节炎膝关节钙化软骨和软骨下骨的矿物质晶体厚度

骨关节炎（OA）是全球最常见的关节疾病。在 OA 中，关节软骨退化通常伴随着软骨下骨的硬化。然而，目前尚不清楚在纳米结构水平上 OA 与组织矿化之间的关联。特别是，识别钙化软骨在技术上具有挑战性，其中发生相关但知之甚少的病理过程，如潮汐标记增殖和进步。在这里，我们使用具有 5μm 高空间分辨率的最先进的微焦点小角度 X 射线散射来确定人类软骨下骨和钙化软骨中的矿物晶体厚度。从内侧间室膝关节 OA 患者 (n=15) 和尸体膝关节 (n=10) 的内侧和外侧间室获得具有广泛 OA 严重程度的样本。首次，我们确定了与病理性潮汐标记增殖相关的明确定义的钙化软骨层，与其余钙化软骨相比，它含有 0.32 纳米厚的晶体。此外，我们发现与健康膝关节相比，OA 外侧隔室的两个组织中的矿物晶体都厚 0.2nm，表明外侧隔室在内侧隔室膝关节 OA 中的负荷通常较小，因此表明存在负荷相关的疾病过程。此外，软骨下骨的晶体厚度随着组织病理学 OA 严重程度的增加而降低。总之，我们报告了 OA 期间矿物晶体厚度的新变化。我们的数据表明，膝关节的卸载与矿物晶体的生长有关，这在钙化软骨中尤为明显。在软骨下骨中，