Single-cell RNA-Seq Analysis Reveals the Role of Endochondral Ossification in Promoting the Intervertebral Disc Degeneration

Intervertebral Disc Degeneration (IDD) is the most common cause of spinal disorders. Changes in the phenotype of nucleus pulposus cells lead to various tissue alterations and play a decisive role in the progression of IDD through complex interactions, but the specific mechanisms of phenotypic differentiation have remained elusive. In their single-cell sequencing results, the authors have identified a subgroup of nucleus pulposus cells with increased expression of osteogenic markers during the degeneration process. They have further mapped the cell differentiation fate trajectory of nucleus pulposus cells toward osteogenesis and validated through various experiments that this differentiation fate is a direct factor causing IDD. Meanwhile, within the inflammatory microenvironment, a novel group of GPNMB+ macrophages may significantly accelerate this differentiation process.Deciphering the specific molecular mechanisms underlying the promotion of nucleus pulposus cell osteogenic differentiation fate can provide a completely new theoretical foundation and a precise targeted therapeutic landscape for understanding the pathogenesis of IDD.