title: Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation.
abstract: Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors, is a rheumatic disease with the highest prevalence, representing a severe health burden with a tremendous economic impact. Members of the nuclear factor κB (NF-κB) family orchestrate mechanical, inflammatory and oxidative stress-activated processes, thus representing a potential therapeutic target in OA disease. The two pivotal kinases, IκB kinase (IKK) α and IKKβ, activate NF-κB dimers that might translocate to the nucleus and regulate the expression of specific target genes involved in extracellular matrix remodelling and terminal differentiation of chondrocytes. IKKα, required for the activation of the so-called non-canonical pathway, has a number of NF-κB-independent and kinase-independent functions in vivo and in vitro, including controlling chondrocyte hypertrophic differentiation and collagenase activity. In this short review, we will discuss the role of NF-κB signalling in OA pathology, with emphasis on the functional effects of IKKα that are independent of its kinase activity and NF-κB activation.
authors.affiliation: Laboratory RAMSES-Research, Innovation & Technology Department , Rizzoli Orthopedic Research Institute , Bologna , Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Olivotto
authors.affiliation: Research Division , Hospital for Special Surgery and Weill Cornell Medical College , New York , USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.affiliation: Biochemistry and Cell Biology Department , Stony Brook University , Stony Brook , USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Marcu
authors.affiliation: Research Division , Hospital for Special Surgery and Weill Cornell Medical College , New York , USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
keywords: Chondrocytes; Cytokines; Inflammation; Osteoarthritis