GOLGB1 deficiency accelerates intervertebral disc degeneration by activating the MAPK pathway.

Intervertebral disc degeneration (IDD) is a multifactorially regulated age-related condition. Golgin B1 (GOLGB1) is a large Golgi-related transmembrane protein encoded by golgb1 gene. Since its discovery, GOLGB1 has been proved to be related to many diseases. However, its role in IDD is still unclear. The aim of this research was to examine whether GOLGB1 deficiency accelerates disc degeneration and to study its mechanism. We selected C57BL/6 male mice aged 8 weeks to isolate, culture and identify nucleus pulposus (NP) cells, and used a variety of experimental techniques, including plasmid transfection, western blotting (WB), real-time fluorescence quantitative PCR (RT-qPCR), EdU staining, Tunnel staining, CCK8 and flow cytometry (FCM) to detect the effects of GOLGB1 on the degeneration, proliferation and apoptosis of NP cells in vitro. Then, 8-week-old C57BL/6 male mice were selected for caudal vertebra acupuncture to establish IDD model, and the role and mechanism of GOLGB1 in the development of IDD were studied by HE staining, Safranin O-Fast Green staining, Alcian Blue staining and immunohistochemistry (IHC) staining. Our results demonstrated lower expression of GOLGB1 in human tissues with NP degeneration. Additionally, GOLGB1 expression was reduced in NP tissue from aging adult mice and IDD model mice. We further verified that GOLGB1 knockdown worsened NP cell degeneration, disturbed the composition of the extracellular matrix (ECM), and upset the harmony between anabolism and catabolism. Moreover, GOLGB1 knockdown inhibited the proliferation of NP cells and increased the apoptosis of NP cells. Mechanistically, GOLGB1 knockdown elevated p-ERK and p-P38 levels and activated the MAPK pathway. A MAPK signaling pathway inhibitor (SCH772984) strongly reversed this phenomenon and rescued the degeneration of NP cells. These findings suggest that GOLGB1 may be a potential new target for IDD. GOLGB1 is a protective factor against disc degeneration, and knockdown of GOLGB1 accelerates IDD by activating the MAPK pathway.