Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation

摘要: Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived tissue-derived factors, is rheumatic with the highest prevalence, representing severe health burden tremendous economic impact. Members of nuclear factor κB (NF-κB) family orchestrate mechanical, inflammatory oxidative stress-activated processes, thus potential therapeutic target in OA disease. The two pivotal kinases, IκB kinase (IKK) α IKKβ, activate NF-κB dimers that might translocate to nucleus regulate expression specific genes involved extracellular matrix remodelling terminal differentiation chondrocytes. IKKα, required for activation so-called non-canonical pathway, has number NF-κB-independent kinase-independent functions vivo vitro, including controlling chondrocyte hypertrophic collagenase activity. In this short review, we will discuss role signalling pathology, emphasis on functional effects IKKα are independent its activity activation.