Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis

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.

cartilage; cathepsin K; chondrocyte; inflammation; joint; osteoarthritis; proteolytic enzymes.