Journal of Inflammation Research (Feb 2024)
Pyroptosis in Osteoarthritis: Molecular Mechanisms and Therapeutic Implications
Abstract
Yeping Chen,1,* Daofu Zeng,1,* Guizheng Wei,1,* Zhidong Liao,1,2 Rongyuan Liang,1 Xiajie Huang,1,2 William W Lu,3 Yan Chen1,2 1Department of Bone and Joint Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Orthopedics and Traumatology, the University of Hong Kong, Hong Kong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Chen, Department of Bone and Joint Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Tel +86-18077790338, Email [email protected]: Osteoarthritis (OA) is a chronic disease that causes pain and functional impairment by affecting joint tissue. Its global impact is noteworthy, causing significant economic losses and property damage. Despite extensive research, the underlying pathogenesis of OA remain an area of ongoing investigation. It has recently been discovered that the OA progression is significantly influenced by pyroptosis. Pyroptosis is a complex process that involves three pathways culminating in the assembly of Gasdermin-D (GSDMD)-N-terminal (GSDMD-NT) into pores through aggregation on the plasma membrane. The aggregation of GSDMD-NT proteins stimulates the release of inflammatory mediators, such as Interleukin-1β (IL-1β), Interleukin-18 (IL-18), and Matrix Metallopeptidase 13 (MMP13), ultimately leading to cellular lysis. The pyroptosis process in specific cells, including synovial macrophages, fibroblast-like synoviocytes (FLS), chondrocytes, and subchondral osteoblasts, contributs factor to the development of OA. Currently, the specific cells that undergo pyroptosis first are not yet fully understood, and it remains unknown whether pyroptosis in one cell can trigger the same process in other cells. Therefore, targeting pyroptosis could potentially offer a novel treatment approach for OA patients. We present a comprehensive analysis of the molecular mechanisms and key features of pyroptosis. We also outline the current research progress on various aspects, including synovial tissue, articular cartilage, extracellular matrix (ECM), and subchondral bone, with a focus on pyroptosis. The aim is to provide theoretical references for the effective management of OA.Keywords: pyroptosis, osteoarthritis, caspases-1/4/5/11, GSDMD, synovium, chondrocytes
