Stage-specific and location-specific cartilage calcification in osteoarthritis development
Stage-specific and location-specific cartilage calcification in osteoarthritis development
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DOI：
10.1136/ard-2022-222944
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发表时间：
2022-10
影响因子：
27.4
通讯作者：
Xiaozhao Wang;Qin Wu;Ru Zhang;Zhang Fan;Wenyue Li;Renwei Mao;Zihao Du;Xudong Yao;Yuanzhu Ma;Yiming Yan;Wei Sun;Hongwei Wu;Wei Wei-Wei;Yejun Hu;Yi Hong;Huan Hu;Yiwen Koh;Wangping Duan;Xiao Chen;H. Ouyang
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文献类型：
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作者：
Xiaozhao Wang;Qin Wu;Ru Zhang;Zhang Fan;Wenyue Li;Renwei Mao;Zihao Du;Xudong Yao;Yuanzhu Ma;Yiming Yan;Wei Sun;Hongwei Wu;Wei Wei-Wei;Yejun Hu;Yi Hong;Huan Hu;Yiwen Koh;Wangping Duan;Xiao Chen;H. Ouyang
目的通过多种纳米分析技术研究骨关节炎（OA）软骨中矿物质的阶段特异性和位置特异性沉积及其特征。方法采用显微CT、扫描电镜结合能谱、显微拉曼光谱、聚焦离子束扫描电镜、高分辨电子能量损失谱结合透射电镜、纳米压痕和原子力显微镜等技术对正常和OA软骨进行连续切片，分析OA软骨的结构、成分和力学特性。结果我们发现OA的进展既有关节表面自上而下的钙化，也有骨软骨界面自下而上的钙化。自上而下的钙化过程开始于早期OA（OA-E）期间关节表面中的球形矿物颗粒形成，随后是晚期OA（OA-A）期间纤维形成和密集堆积的材料转化深入软骨。OA-E中自下而上的钙化开始于在原始钙化软骨上方形成过多的钙化组织层，表现出钙化的三明治结构。随着时间的推移，钙化软骨的原始层和上层融合，从而使钙化软骨区域增厚并破坏软骨结构。在OA-E期间，钙化软骨过度矿化，含有更硬的碳酸化羟基磷灰石（HAp）。在OA-A期间，它是低矿化的，含有较软的HAp。这种差异可能归因于OA-E期间的基质囊泡成核和OA-A期间的碳酸盐核心。结论这项工作完善了我们目前对OA进展机制的理解，并为OA中特定位置软骨钙化特征的建立提供了潜在的治疗靶向策略。
Objectives This study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies. Methods Normal and OA cartilages were serially sectioned for micro-CT, scanning electron microscopy with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, focused ion beam scanning electron microscopy, high-resolution electron energy loss spectrometry with transmission electron microscopy, nanoindentation and atomic force microscopy to analyse the structural, compositional and mechanical properties of cartilage in OA progression. Results We found that OA progressed by both top-down calcification at the joint surface and bottom-up calcification at the osteochondral interface. The top-down calcification process started with spherical mineral particle formation in the joint surface during early-stage OA (OA-E), followed by fibre formation and densely packed material transformation deep into the cartilage during advanced-stage OA (OA-A). The bottom-up calcification in OA-E started when an excessive layer of calcified tissue formed above the original calcified cartilage, exhibiting a calcified sandwich structure. Over time, the original and upper layers of calcified cartilage fused, which thickened the calcified cartilage region and disrupted the cartilage structure. During OA-E, the calcified cartilage was hypermineralised, containing stiffer carbonated hydroxyapatite (HAp). During OA-A, it was hypomineralised and contained softer HAp. This discrepancy may be attributed to matrix vesicle nucleation during OA-E and carbonate cores during OA-A. Conclusions This work refines our current understanding of the mechanism underlying OA progression and provides the foothold for potential therapeutic targeting strategies once the location-specific cartilage calcification features in OA are established.