2023, Vol. 27 ›› Issue (36): 5884-5890

Roles of ferroptosis in intervertebral disc degeneration and osteoarthritis

Xiong Zhilin, Sun Hong, Liu Miao, Zhuang Yong   

Abstract: BACKGROUND: Ferroptosis is a new type of programmed cell death, distinguished from apoptosis, autophagy and pyroptosis, which is characterized by the iron-dependent accumulation of polyunsaturated fatty acid peroxidation. Studies in recent years have shown that ferroptosis is closely associated with the development of intervertebral disc degeneration and osteoarthritis.
OBJECTIVE: To review the action mechanism of ferroptosis and its role in intervertebral disc degeneration and osteoarthritis progression, and provide new therapeutic strategies for intervertebral disc degeneration and osteoarthritis.
METHODS: PubMed, WanFang and CNKI databases were used as the literature sources. The search terms were “intervertebral disc degeneration; osteoarthritis; nucleus pulposus; chondrocytes; articular cartilage; ferroptosis” in English and Chinese. Finally, 67 articles were screened for this review.
RESULTS AND CONCLUSION: (1) Ferroptosis is a newly discovered programmed cell death, whose mechanism is closely related to the factors such as abnormal iron ion accumulation, polyunsaturated fatty acid peroxidation, abnormal amino acid metabolism, mitochondrial dysfunction, and ferritin autophagy. (2) Various stimulation factors such as homocysteine, tert-buty1 hydroperoxide and ferric ammonium citrate mainly through inhibiting glutathione peroxidase 4 activity cause ferroptosis of nucleus pulposus cells, annulus fibrosus cells, and chondrocytes of the endplate chondrocytes, thus promoting intervertebral disc degeneration. In addition, the role of ferroptosis in intervertebral disc degeneration is regulated by miRNA. (3) Ferroptosis promotes the progression of osteoarthritis by participating in chondrocyte loss, extracellular matrix lysis, and synovitis. Chondrocyte ferroptosis is inhibited by stigmasterol, D-mannose, astaxanthin, metformin and icariin, while it is exacerbated by interleukin-1β, ferric ammonium citrate and RNA binding protein SND1. (4) The therapeutic effects of some drugs targeting ferroptosis, such as deferoxamine, ferroptosis inhibitor, on intervertebral disc degeneration and osteoarthritis, have been verified by experiment, but have not been applied clinically. With the deepening of research, inhibiting the occurrence of ferroptosis can provide a new and effective strategy for the treatment and prevention of intervertebral disc degeneration and osteoarthritis.

Key words: ferroptosis, intervertebral disc degeneration, osteoarthritis, oxidative stress, lipid peroxidation, chondrocyte, nucleus pulposus cell, annulus fibrosus cell