Given that aberrant mechanical stress is a significant contributor to CEP degeneration and IDD progression,40 we next evaluate the roles of OPN in a mechanical stress model induced by intermittent cyclic mechanical tension (ICMT), which is a common way to mimic the in vivo mechanical strain experienced by EPCs.41 The results showed that both TNF-α and ICMT treatments could significantly decrease the expression level of OPN while increasing the protein levels of NLRP3 and p-p65, and these trends were more obvious following co-treatment with TNF-α and ICMT (Fig. S4E). Here, SPP1 is linked to intervertebral disk degenerative disorder.