Upregulated CEMIP promotes intervertebral disc degeneration via AP‐1‐mediated change in chromatin accessibility

Integrative ATAC-seq and transcriptional profiling revealed CEMIPas a key biomarker and contributor to IDD, exhibiting marked upregulation in IDD. Further, we demonstrated that the AP-1 family, especially, c-Fos, orchestrates the upregulation of CEMIP. Elevated CEMIP plasma levels correlated with clinical IDD severity, and CEMIP knockout mice demonstrated improved IDD. Mechanistically, CEMIP disrupted extracellular matrix homeostasis through its regulation of high molecular weight hyaluronic acid degradation, and its contribution to fibrotic changes. Our findings offer new avenues for IDD treatment strategies, with the potential to alleviate the global burden of back pain.