EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts

Background/aim: Epidermal growth factor receptor (EGFR) family members and their associated ligands may be related to bone and joint destruction in rheumatoid arthritis. Matrix metalloproteinases are responsible for joint and bone tissue degradation. This study is intended to investigate the effect of epidermal growth factor receptor inhibition by lapatinib on the synthesis of matrix metalloproteinases in in vitro. Materials and methods: Synovial fibroblast cell culture was obtained from a patient with rheumatoid arthritis who underwent knee arthroplasty. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were added to the cell culture to stimulate synovial fibroblast cells and create an inflammatory character. Understimulated and nonstimulated conditions, lapatinib was applied to the culture in four different concentrations of 25, 50, 100, and 200 mu mol. Then, matrix metalloproteinase -1, -3, and, -13 levels were assessed. Results: When stimulated with IL-1 beta and TNF-alpha, the synthesis of matrix metalloproteinases from synovial fibroblast was increased significantly. When lapatinib is added to the stimulated synovial fibroblasts, matrix metalloproteinases synthesis is significantly suppressed. Conclusion: Inhibition of the EGFR pathway with lapatinib suppresses matrix metalloproteinases synthesis. Our results suggest EGFR pathway inhibition may be a promising option to prevent joint destruction in the treatment of rheumatoid arthritis.

Automated summary

This study investigates the effect of lapatinib, an inhibitor of epidermal growth factor receptor (EGFR), on the synthesis of matrix metalloproteinases in rheumatoid arthritis. The results show that lapatinib significantly suppresses the synthesis of matrix metalloproteinases, suggesting that inhibition of the EGFR pathway may be a promising option to prevent joint destruction in the treatment of rheumatoid arthritis.