TNF and osteoarthritis: Additional therapeutic benefits of GPR4 antagonism have been reported in tissue ischemia, myocardial infarction, chronic obstructive pulmonary disease (COPD), and osteoarthritis models, reducing proinflammatory molecules such as VCAM-1, E-selectin, IL-17, interferon-γ, TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), Mucin5AC, matrix metalloprotease (MMP)-9, MMP-12, and NF-κB [22,45,47,50,59].