Cartilage Intermediate Layer Protein‐1 Promotes Extracellular Matrix Degeneration via Interacting With <scp>CD47</scp>

Intervertebral Disc Degeneration (IDD) is a multifactorial result contributing to Low Back Pain (LBP) while Cartilage Intermediate Layer Protein-1 (CILP-1) is gradually up-regulated along with IDD. Whether CILP-1 acts in a direct role promoting IDD via regulating matrix metabolism remains to be elucidated. Herein, we firstly detected the expression level of matrix-related phenotypes in nucleus pulposus (NP) cells treated with CILP-1, including ADAMTS, MMPs, IL-6, Collagens, Aggrecan (ACAN) and SOX9. Meanwhile, the phosphorylation levels of MAPKs and NF-κB were detected to explore the involved signalling pathways, which were further validated by inhibition experiments. Furthermore, molecular docking analysis was employed to evaluate the possibility of CD47 acting as the direct receptor mediating CILP's regulation above, which was further validated by immunoprecipitation and inhibition experiment. Our findings have made a comprehensive investigation into the regulatory effect of CILP-1 on the matrix metabolism of NP cells and explored the underlying mechanism.