Similar to our observations, IL-6 has been reported to promote GAG synthesis in fibroblasts.56 Conversely, the persistent elevation of IL-6 and other inflammatory factors is linked to chronic painful intervertebral disc diseases and promotes ECM catabolism.57–59 Our data here suggest that the TRPV4-dependent activation of IL-6 results in a net increase in GAGs between these known anabolic and catabolic functions. Here, IL6 is linked to intervertebral disk degenerative disorder.