In middle-aged and older adults, intervertebral disc degeneration (IDD) is a major cause of chronic low back pain and disability. This pathological process is closely linked to the activation of inflammatory factors resulting from an imbalance in extracellular matrix (ECM) metabolism and abnormalities in Nucleus pulposus cells (NPCs). This study aims to clarify the functional importance of LINC00963 in IDD and its potential molecular mechanisms. 102 IDD patients and 88 scoliosis controls were enrolled. IL-1β-stimulated NPCs modeled IDD in vitro. RT-qPCR detected LINC00963, miR-1252-5p, MAPK1, ECM markers (Col-II, Aggrecan, MMP3, and MMP13), and ELISA measured inflammatory cytokines (IL-6, TNF-α, and IL-1β). ROC assessed LINC00963’s diagnostic value. ENCORI predicted the LINC00963-miR-1252-5p binding and the miR-1252-5p-MAPK1 binding, which were confirmed by DLR and RIP assays. In IDD patients and in vitro models, LINC00963 was upregulated, while miR-1252-5p was downregulated. LINC00963 overexpression increased inflammatory cytokines (IL-6, TNF-α, IL-1β) and ECM degradation (MMP3/13), while suppressing Col-II and Aggrecan. miR-1252-5p, a direct target of LINC00963, reversed these effects, inhibiting inflammation and ECM degradation. MAPK1 is a downstream target of miR-1252-5p. Downregulation of LINC00963 can promote the expression of miR-1252-5p, inhibit inflammatory responses, weaken ECM degradation, and promote matrix synthesis, thereby effectively delaying the pathological process of IDD.
Wei et al. (Tue,) studied this question.
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