Role of Cathepsin K in Normal Joints and in the Development of Arthritis

Abstract

Cysteine cathepsins are a large family of proteolytic enzymes active at acidic pH as found in lysosomes. Since its discovery in 1990's, cathepsin K has been shown to be a key enzyme in osteoclastic bone resorption through its activity in the resorption lacuna. Although characteristic to osteoclasts, the expression of cathepsin K has also been observed at other sites in skeleton. Several recent observations have demonstrated up-regulation of cathepsin K in osteoarthritic cartilage and inflamed synovial tissue. As cathepsin K is one of the few extracellular proteolytic enzymes capable of degrading native fibrillar collagen, it may play an important role in the progressive destruction of articular cartilage both in osteoarthritis and in inflammatory arthritides. Also transgenic mouse models have provided evidence supporting the important role of cathepsin K in both groups of arthritides. The aim of this chapter is to review the accumulating evidence for the role of cathepsin K in degradation of articular cartilage regardless of its pathogenic background, and to discuss the potential efficacy of cathepsin K inhibitors to slow down or prevent articular cartilage degradation.

Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype

“…Several studies have also demonstrated the upregulation of this cysteine protease in cartilage and synovium of inflamed joints, and it is believed to play an important role in the destruction of articular cartilage (reviewed in [44]). In the present study, cathepsin K transcription levels were elevated in synovial tissue in response to carrageenan-induced inflammation.…”

Trichostatin A inhibits expression of cathepsins in experimental osteoarthritis

“…Recent studies showed that cysteine proteases especially cysteine cathepsins were also involved in the degradation of cartilage matrix [3,4]. Among them, cathepsin K received main attention as it is capable to cleave type I and II collagens as well as aggrecan [5,6]. Elevated gene expression of cathepsin K has been noted in articular cartilage in transgenic mouse for OA, supporting the correlation between cathepsin K and OA [7].…”

Novel selective MMP-13 inhibitors reduce collagen degradation in bovine articular and human osteoarthritis cartilage explants

“…The disease is characterized by a high degree of clinical and pathophysiological heterogeneity. The destruction of cartilage in arthritic conditions is believed to be catalyzed by matrix metalloproteases (MMPs), aggrecanases, and probably cathepsins [2][3][4][5][6][7].…”