The gene expression of caspase 3, matrix metalloproteinase-9, tissue inhibitor of metalloproteinases-1, and cathepsins S and K in patients with osteoarthritis requiring large joint replacement

Abstract

Osteoarthritis (OA) is a chronic rheumatic disease that is characterized by pain and articular cartilage degradation. Pain in OA is a main clinical symptom that limits working capacity and is one of the indications for joint replacement. However, 10-40% of patients with OA also continue to experience painful sensations after surgery.Objective: to develop a method for searching for biomarkers to predict the dynamics of pain in the postoperative period and to determine the feasibility of arthroplasty on the basis of a retrospective analysis of relative blood gene expression prior to surgery.Patients and methods. The investigators tested the blood taken from 53 OA patients (mean age, 56.5±8.9 years) before knee arthroplasty and from 26 healthy donors (mean age, 55±8.3 years). Total RNA was isolated from blood and after reverse transcription into complementary DNA was used to measure the level of relative gene expression in real-time polymerase chain reaction.Results and discussion. A retrospective analysis of the expression of genes associated with central sensitization in 53 patients with OA before arthroplasty showed that the data on the expression of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and transforming growth factor β1 were uninformative due to their high blood expression in all the patients. The high gene expression of cathepsin S (in 17% of the patients) and cathepsin K (in 21%) and the low gene expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) (in 31%) may indicate that postoperative pain can be persistent. In contrast, no post-arthroplasty pain can be expected in 43% OA patients with low caspase 3 expression and in 23% of those with low MMP-9 one.Conclusion. Analysis of pre-arthroplasty blood gene expression in patients with OA seems to be a promising approach to predicting the dynamics of pain after surgical treatment.

Keywords

• osteoarthritis
• pain
• gene expression
• peripheral blood
• prediction of arthroplasty outcome