Abstract
Links between cathepsin K and the pathophysiology of osteoarthritis (OA) can be established, not least because of the overabundance of cathepsin K in the serum of OA patients and the upregulation of cathepsin K in degraded cartilage in animal models of OA. Chondrocytes, chondroclasts, or osteoclasts contribute to the accumulated cathepsin K at the diseased osteochondral junction. After a general presentation of OA and cartilage physiology, as well as its degradation processes, we describe the function of cathepsin K and its effect on cartilage degradation via type II collagen cleavage. An overview of the most promising cathepsin K inhibitors is then presented, together with their in vitro effects. Although intensive research on cathepsin K inhibitors initially focused on bone resorption, there is growing interest in the potential of these drugs to prevent cartilage degradation. In this review, we summarize the pre-clinical and clinical trials that support the use of cathepsin K inhibitors in the treatment of OA. To date, no molecules of this type are commercially available, although a few have undergone clinical trials, but we believe that the development of cathepsin K inhibitors could broaden the therapeutic arsenal for the treatment of OA.