MIF inhibition attenuates intervertebral disc degeneration by reducing nucleus pulposus cell apoptosis and inflammation

Zhongchen Dong; Peng Yang; Zhongwei Ji; Chunyang Fan; Jiale Wang; Pengfei Zhu; Feng Zhou; Minfeng Gan; Xiexing Wu; Dechun Geng

doi:10.1016/j.yexcr.2024.114089

MIF inhibition attenuates intervertebral disc degeneration by reducing nucleus pulposus cell apoptosis and inflammation

Exp Cell Res. 2024 May 11;439(1):114089. doi: 10.1016/j.yexcr.2024.114089. Online ahead of print.

Authors

Zhongchen Dong¹, Peng Yang², Zhongwei Ji³, Chunyang Fan², Jiale Wang², Pengfei Zhu², Feng Zhou⁴, Minfeng Gan⁵, Xiexing Wu⁶, Dechun Geng⁷

Affiliations

¹ Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China; Wujin Hospital Affiliated Hospital, Jiangsu University, Changzhou, Jiangsu, China.
² Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
³ Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China; Center for Rehabilitation Medicine, Department of Pain Management, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
⁴ Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. Electronic address: liw72@126.com.
⁵ Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. Electronic address: spineganmf@126.com.
⁶ Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. Electronic address: wuxiexing@163.com.
⁷ Orthopaedic Institute, Department of Orthopaedic Surgery, the First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. Electronic address: szgengdc@suda.edu.cn.

PMID: 38740166
DOI: 10.1016/j.yexcr.2024.114089

Abstract

Nucleus pulposus cells (NPCs) apoptosis and inflammation are the extremely critical factors of intervertebral disc degeneration (IVDD). Nevertheless, the underlying procedure remains mysterious. Macrophage migration inhibitory factor (MIF) is a cytokine that promotes inflammation and has been demonstrated to have a significant impact on apoptosis and inflammation. For this research, we employed a model of NPCs degeneration stimulated by lipopolysaccharides (LPS) and a rat acupuncture IVDD model to examine the role of MIF in vitro and in vivo, respectively. Initially, we verified that there was a significant rise of MIF expression in the NP tissues of individuals with IVDD, as well as in rat models of IVDD. Furthermore, this augmented expression of MIF was similarly evident in degenerated NPCs. Afterwards, it was discovered that ISO-1, a MIF inhibitor, effectively decreased the quantity of cells undergoing apoptosis and inhibited the release of inflammatory molecules (TNF-α, IL-1β, IL-6). Furthermore, it has been shown that the PI3K/Akt pathway plays a vital part in the regulation of NPCs degeneration by MIF. Ultimately, we showcased that the IVDD process was impacted by the MIF inhibitor in the rat model. In summary, our experimental results substantiate the significant involvement of MIF in the degeneration of NPCs, and inhibiting MIF activity can effectively mitigate IVDD.

Keywords: Apoptosis; Inflammation; Intervertebral disc degeneration; Macrophage migration inhibitory factor; Nucleus pulposus cell.