Table 1

Summary of the contribution of IKKα and IKKβ to chondrocyte catabolism and cartilage degradative processes

Contribution of IKKα and IKKβ to chondrocyte catabolism and cartilage degradation	References
Controls MMP, PGE2, COL10 and NO expression induced by RAGE	26–28
Participates in the TLR-driven MMP expression and NO production	29^, 30
Regulates the expression of mediators of inflammation: ELF3, NOS2, IL-1, COX2	5^, 15^, 16^, 25^, 31
Links inflammation and hypertrophic-like conversion via HIF-2α, RUNX2, C/EBPβ	18^, 19^, 32
Perpetuates cartilage damage modulating signals driven by ECM products	33–38
Triggers inappropriate differentiation via IL-8 and GROα modulation	39–41
Decreases SOX9 expression and activity leading to abnormal matrix production and phenotype	42 43
Controls MAPK signalling, ECM remodelling, apoptosis and hypertrophy via GADD45β	44–46
Controls aggrecanase activity (ADAMTS5 expression) during OA development	47
Modulates collagenase activity via IKKα-mediated control of MMP10 and TIMP3*	42^, 48
Hypertrophic-like conversion via IKKα control of RUNX2, COL10 and VEGF-A expression*	42^, 48

*Indicates contribution of IKKα (via kinase-independent actions).
C/EBPβ, CCAAT-enhancer-binding protein beta; ECM, extracellular matrix; ELF3, E74-like factor 3; GROα, chemokine (C-X-C motif) ligand 1; HIF-2α, endothelial PAS domain protein 1 (hypoxia inducible factor 2 alpha); IKKα, IκB kinase alpha; IL-1, interleukin 1; MAPK, mitogen-activated protein kinase; MMP, metalloproteinases; NOS2, nitric oxide synthase 2, inducible; OA, Osteoarthritis; RAGE, advanced glycosylation end product-specific receptor; SOX9, SRY (sex determining region Y)-box 9; TIMP3, tissue inhibitor of MMP 3; TLR, toll-like receptor; VEGF-A, vascular endothelial growth factor A.