RBPJ and osteoarthritis: Any such role is likely to be negative since genetic activation of the Notch pathway in cartilage for a prolonged period causes degeneration of this tissue in a manner dependent on IL6.63 At the same time, ablation of the key downstream component of the Notch pathway, RBP-Jk, protects the joint from surgery-induced osteoarthritis62 but results in age-dependent osteoarthritis.64 It appears plausible that surgical induction of osteoarthritis activates Notch signaling throughout the cartilage,62 but in mice lacking RBP-Jk, this elevation of Notch activity is abrogated.