Stage-specific and location-specific cartilage calcification in osteoarthritis development. Issue 3 (19th October 2022)

• Record Type: Journal Article
• Authors: Wang, Xiaozhao; Wu, Qin; Zhang, Ru; Fan, Zhang; Li, Wenyue; Mao, Renwei; Du, Zihao; Yao, Xudong; Ma, Yuanzhu; Yan, Yiyang; Sun, Wei; Wu, Hongwei; Wei, Wei; Hu, Yejun; Hong, Yi; Hu, Huan; Koh, Yi Wen; Duan, Wangping; Chen, Xiao; Ouyang, Hongwei
• Is Part Of: Annals of the rheumatic diseases. Volume 82:Issue 3(2023)
• Page Start: 393
• Page End: 402
• Publication Date: 2022-10-19
• Subjects: osteoarthritis -- osteoarthritis, Knee -- crystal arthropathies; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard-2022-222944
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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.