Moreover, treatment with both CAPE and MCC950 protected against the TNF-α-induced inflammation in OPN-deficient EPCs and attenuated CEP degeneration in cKO mice following LSI, implying that the NLRP3 inflammasome might also be regulated by other pathways, besides the NF-κB, including the mTOR and FOXO3a signaling and others.83,84 Notably, OPN can inhibit the NLRP3 inflammasome activity in other disease models.85,86 Therefore, clarifying the relationship between OPN and NLRP3 may provide new insights into the OPN regulation on CEP homeostasis, thereby developing biomedical treatments for IDD. The gene discussed is FOXO3; the disease is intervertebral disk degenerative disorder.