The intra-articular treatment options today are limited to intra-articular steroids with only transient anti-inflammatory effects. Other options such as radiochemical synovectomy with radio-active isotopes or osmic acid are not easily or not at all available. Our results show that local intra-articular treatment with the administration of a PUMA-expressing vector represents an efficient strategy for the control of abnormal synoviocyte proliferation. In addition to the local protective effect, the control of local inflammation appears to have a systemic effect. Nevertheless, this apoptosis-based therapeutic strategy has potential as an alternative to surgical or radiochemical synovectomy in a long list of arthritis conditions including RA, mono- or oligo-articular arthritis which includes juvenile oligo articular arthritis, inflammatory osteoarthritis, or the orphan disease pigmented-villo-nodular synovitis. A first proof of concept trial to treat this cancer-like disease by inducing targeted cell death may help in preventing the high rate of recurrences.