TNF and osteoarthritis: In response to endogenous or exogenous inflammatory cytokines (IL-1β and TNF-α), IKKβ is activated first, leading to phosphorylation of IκBα protein which degraded through ubiquitination which releases NF-κB dimer into the nucleus binding to specific DNA sequences and promote transcription of inflammatory factors, chemokines, and metalloproteinases promoting the progression of osteoarthritis [53, 54].