Pyroptosis and Intervertebral Disc Degeneration: Mechanistic Insights and Therapeutic Implications

Yuying Ge; Yuying Chen; Chijiao Guo; Huan Luo; Fangda Fu; Weifeng Ji; Chengliang Wu; Hongfeng Ruan

doi:10.2147/JIR.S382069

Pyroptosis and Intervertebral Disc Degeneration: Mechanistic Insights and Therapeutic Implications

J Inflamm Res. 2022 Oct 17:15:5857-5871. doi: 10.2147/JIR.S382069. eCollection 2022.

Authors

Yuying Ge^#¹, Yuying Chen^#², Chijiao Guo^#¹, Huan Luo³, Fangda Fu^{1

4}, Weifeng Ji^{1

4}, Chengliang Wu^{1

4}, Hongfeng Ruan^{1

4}

Affiliations

¹ The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
² The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
³ Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
⁴ Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People's Republic of China.

^# Contributed equally.

Abstract

Low back pain (LBP) is a common problem worldwide, resulting in great patient suffering and great challenges for the social health system. Intervertebral disc (IVD) degeneration (IVDD) is widely acknowledged as one of the key causes of LBP. Accumulating evidence suggests that aberrant pyroptosis of IVD cells is involved in the pathogenesis of IVDD progression, however, the comprehensive roles of pyroptosis in IVDD have not been fully established, leaving attempts to treat IVDD with anti-pyroptosis approaches questionable. In this review, we summarize the characteristics of pyroptosis and emphasize the effects of IVD cell pyroptosis on the pathological progression of IVDD, including secretion of cytokines, nucleus pulposus cell apoptosis and autophagy, accelerated extracellular matrix degradation, annulus fibrosus rupture, cartilage endplate calcification, vascularization, sensory and sympathetic fiber neoinnervation, and infiltrating lymphatic vessels. Finally, we discuss several interventions used to treat IVDD by targeting pyroptosis. This review provides novel insights into the crucial role of IVD cell pyroptosis in IVDD pathogenesis, and could be informative for developing novel therapeutic approaches for IVDD and LBP.

Keywords: anti-pyroptotic approach; inflammasome; intervertebral disc degeneration; low back pain; pyroptosis.

Publication types

Review

Grants and funding

This work was financially supported by National Natural Science Foundation of China (No.: 82174140, 82174401, 81973870), Natural Science Foundation of Zhejiang Province (No.: LY22H270003), the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China under Grant No. LBY22H270008, Traditional Chinese Medical Administration of Zhejiang Province (No.: 2022ZX005, 2022ZB119, 2021ZB090), Zhejiang Medical and Health Science and Technology Project (No.: 2023RC194, 2021KY222), Research Project of Zhejiang Chinese Medical University Scientific (No.: 2021JKZDZC02, 2021JKZKTS036A, 2021JKJNTZ022B, 2019ZG25), Research Project of Zhejiang Chinese Medical University (No.: 2021JKZDZC02, 2021JKZKTS036A, 2021JKJNTZ022B), National Undergraduate Innovation and Entrepreneurship Training Program (No.: 202210344006, 202210344028, 202210344037, 202210344064, 202110344005, 202110344025, S202110344007, 202010344004), General Research Project of Zhejiang Provincial Education Department “Special Project for the Reform of Cultivation Mode of Professional Degree Graduate Students in Higher Education Institutions” (No.: Y202145932), Postgraduate Science Research Fund of Zhejiang Chinese Medical University (No.: 2021YKJ02, 2020YKJ07), The Science and Technology Innovation Program for College Students (new talent program) of Zhejiang Province (No.: 2022R410A001, 2022R410A009, 2022R410A018).