Repeated injections of TNF-α into the joints of TNF-R1 knockout mice enhanced the development of arthritis if such injections were administered during the early phase of arthritis induction but had little effect once the arthritis was established, indicating that TNF-R2 can be involved in the onset of cartilage degradation and degeneration [27]. Here, TNFRSF1A is linked to arthritic joint disease.