Serum Cathepsin K Levels of Patients With Rheumatoid Arthritis
Cathepsin K is a cysteine protease that plays an essential role in osteoclast function and in the degradation of protein components of the bone matrix by cleaving proteins such as collagen type I, collagen type II and osteonectin. Cathepsin K therefore plays a role in bone remodelling and resorption in diseases such as osteoporosis, osteolytic bone metastasis and rheumatoid arthritis. We examined cathepsin K in the serum of 100 patients with active longstanding rheumatoid arthritis. We found increased levels of cathepsin K compared with a healthy control group and found a significant correlation with radiological destruction, measured by the Larsen score. Inhibition of cathepsin K may therefore be a new target for preventing bone erosion and joint destruction in rheumatoid arthritis. However, further studies have to be performed to prove that cathepsin K is a valuable parameter for bone metabolism in patients with early rheumatoid arthritis.

Progressive bone and cartilage destruction in arthritic joints leads to irreversible joint destruction, and subsequently to functional declines and work disability. New biomarkers such as cartilage oligomeric matrix protein, osteoprotegerin or receptor activator of NF-κB ligand have been developed to describe the local bone and cartilage process in affected joints.

Cathepsin K is a cysteine protease that plays an essential role in osteoclast function and in the degradation of protein components of the bone matrix. It is produced by bone resorbing macrophages and synovial fibroblasts, and it cleaves proteins such as collagen type I, collagen type II and osteonectin. Cathepsin K therefore plays a role in bone remodelling and resorption in diseases such as osteoporosis, osteolytic bone metastasis and rheumatoid arthritis (RA).

Cathepsin K is a tissue-specific protease associated with pycnodysostosis, a rare genetic disorder that manifests itself in bone abnormalities such as short stature, acroosteolysis of distal phalanges and skull deformities. Cathepsin K knockout mice develop an osteopetrosis. Inhibition of cathepsin K may therefore prevent bone resorption, as could be demonstrated in bone metastasis from breast cancer. Osteoprotegerin has been shown to inhibit the expression of cathepsin K, the main enzyme involved in bone resorption.

The aim of this study was to measure serum levels of cathepsin K in RA and to prove that cathepsin K is a parameter of bone remodelling and resorption in a nonselected cohort of patients with longstanding RA. This patient group shows a variation of age, inflammatory level and Larsen score. We divided this cohort into different groups, according to age, inflammatory level, disease-modifying antirheumatic drug (DMARD) therapy, radiological progression and disease activity, to verify cathepsin K as an age-independent and laboratory inflammatory parameter-independent protease.