IL-6/YAP1/β-catenin signaling is involved in intervertebral disc degeneration

Yes-associated protein 1 (YAP1) is a transcriptional coactivator and negative regulator of the Hippo pathway. It regulates diverse cellular processes, such as cell proliferation, contact inhibition, and tissue size. However, the role of YAP1 in intervertebral disc degeneration (IDD) remains elusive. Here, we demonstrated that YAP1 was activated by Interleukin 6 (IL-6) through tyrosine phosphorylation in nucleus pulposus cells (NP cells). Overexpression of YAP1 decreased Sox-9, Col-II, aggrecan expression, whereas increased matrix metalloproteinases 13 level. In contrast, knockdown of YAP1 by small interfering RNA (siRNA) showed opposite effects and rescued IL-6 induced NP cells degeneration. In addition, western blot showed that IL-6 treatment increased YAP1 and beta-catenin protein level; co-immunoprecipitation (Co-IP) and immunofluorescence analysis showed that IL-6 enhanced YAP1 and beta-catenin interaction and nuclear accumulation. Knockdown of beta-catenin by siRNA blocked IL-6 treatment or YAP1 overexpression induced degeneration. Moreover, we found that verteporfin, a specific inhibitor of YAP1, effectively alleviated IDD development in rat disks. Taken together, our findings indicated that YAP1 plays an important role in IDD, and beta-catenin is essential for IL-6/YAP1 signaling.