TY - JOUR T1 - Stage-specific and location-specific cartilage calcification in osteoarthritis development JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 393 LP - 402 DO - 10.1136/ard-2022-222944 VL - 82 IS - 3 AU - Xiaozhao Wang AU - Qin Wu AU - Ru Zhang AU - Zhang Fan AU - Wenyue Li AU - Renwei Mao AU - Zihao Du AU - Xudong Yao AU - Yuanzhu Ma AU - Yiyang Yan AU - Wei Sun AU - Hongwei Wu AU - Wei Wei AU - Yejun Hu AU - Yi Hong AU - Huan Hu AU - Yi Wen Koh AU - Wangping Duan AU - Xiao Chen AU - Hongwei Ouyang Y1 - 2023/03/01 UR - http://ard.bmj.com/content/82/3/393.abstract N2 - 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.No data are available. ER -