Pathological progression of osteoarthritis: a perspective on subchondral bone

Abstract

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as “top to bottom.” However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone’s physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the “bottom-up” progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Keywords

osteoarthritis / subchondral bone / OPG/RANKL/RANK / CXCL12/CXCR4

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Acknowledgements

This project was supported by the Traditional Chinese Medicine Rehabilitation Service Capability Enhancement Project (No. Medical 032); the Three-year Action Plan for Shanghai to Further Accelerate the Inheritance, Innovation and Development of Traditional Chinese Medicine (No. ZY (2021-2023)-0201-01); and the Pudong New Area Health System Pudong Famous Traditional Chinese Medicine Training Plan (No. PWRzm2020-15). We thank Editage for the English language editing.

Compliance with ethics guidelines

Conflicts of interest Xuefei Li, Wenhua Chen, Dan Liu, Pinghua Chen, Shiyun Wang, Fangfang Li, Qian Chen, Shunyi Lv, Fangyu Li, Chen Chen, Suxia Guo, Weina Yuan, Pan Li, and Zhijun Hu declare that they have no conflict of interest.

This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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