Interestingly, the absence of DR-3 was not associated with a change in the levels of ADAMTS-5, an aggrecanase responsible for cartilage degradation in osteoarthritis (55), suggesting that DR-3 signaling differentially regulates the levels of some (e.g., MMP-9) but not other cartilage-destroying enzymes at this early time point in the AIA process. This evidence concerns the gene MMP9 and osteoarthritis.