Macrophage Efferocytosis as a Therapeutic Strategy in Intervertebral Disc Degeneration

ABSTRACT In recent years, a growing number of studies have disclosed the substantial role of macrophages—key immune cells—in the pathological process of intervertebral disc degeneration. Researchers have categorised macrophage phenotypes into M1 and M2 polarisation, associating these polarisations with intervertebral disc degeneration. Essentially, macrophage phenotypes can be classified as either pro‐inflammatory or anti‐inflammatory. Induced by diverse factors, these distinct polarisation states exert contrary effects on disc injury and repair. Although numerous studies focus on the polarisation of macrophages and the cytokines they secrete in relation to intervertebral disc degeneration, these studies frequently neglect the relationship between the efferocytosis of macrophages and the progression of intervertebral disc degeneration. Efferocytosis is a specialised procedure in which phagocytes, such as macrophages, engulf and eliminate apoptotic cells. This process is crucial for maintaining tissue homeostasis and resolving inflammation. By effectively clearing these dying cells, efferocytosis helps prevent the release of potentially detrimental cellular contents, thereby facilitating healing and the resolution of inflammation. Simultaneously, macrophages digest the engulfed cell debris and release various cytokines that participate in tissue self‐repair. Therefore, this article presents an overview of the molecular mechanisms connecting macrophages and their efferocytosis activity to intervertebral disc degeneration, explores new directions for the utilisation of macrophages in the treatment of intervertebral disc degeneration, and discusses the future prospects for the development of therapeutic targets.