The role of NOTCH signaling pathway in intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is a prevalent degenerative condition and is recognized as the primary cause of low back pain among the elderly population. IDD can be caused by a variety of factors, including aging, inflammatory stimulation, and oxidative stress. These factors collectively contribute to a reduction in nucleus pulposus (NP) cells and an excessive degradation of the extracellular matrix (ECM), thereby facilitating the progression of IDD. The NOTCH signaling pathway is a highly conserved pathway that conducts downstream signals through interactions between cells, thereby regulating cell proliferation, differentiation, and death. This pathway is essential for maintaining tissue homeostasis. Both in vitro and in vivo studies have shown that the NOTCH signaling pathway can promote cell proliferation, alleviate apoptosis, and regulate ECM metabolism by modulating the expression of key enzymes such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), as well as transcription factors like SOX9, thereby preserving matrix integrity in NP cells. Accordingly, activation of the NOTCH signaling pathway may represent a protective strategy for IDD. This review summarizes the latest findings regarding the potential role of the NOTCH signaling pathway in IDD. The intent is to provide a reference for studies of the NOTCH signaling pathway and IDD.