8th International Conference of Orthopedic Surgeons and Rheumatology

Biography

Biography: Syahida Ahmad

Abstract

Statement of the Problem: Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. Our preliminary findings had shown that the newly synthesized curcumin analogue [2,6-bis(2,5-dimethoxybenzylidene) cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis, PGE₂ synthesis and cyclooxygenase (COX) expression in activated macrophage cells. In this study, we further investigated the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) in vitro.

Methodology & Theoretical Orientation: Synovial fibroblast cells (HIG-82) were cultured in vitro and induced by phorbol-12-myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMPs) and pro-inflammatory cytokines. The protective effects of BDMC33 were evaluated toward MMP activities, pro-inflammatory cytokine expression and nuclear factor kappa-B (NF-kB) activation by using various bioassay methods, including zymography, Western blotting, reverse transcription polymerase chain reaction, immunofluorescence microscopy and electrophoretic mobility shift assay.

Findings: The results showed that BDMC33 significantly inhibited the pro-gelatinase B (pro-MMP-9) and collagenase activities via suppression of MMP-1 in activated SF. In addition, BDMC33 strongly suppressed MMP-3 gene expression as well as inhibited COX-2 and IL-6 pro-inflammatory gene expression. We also demonstrated that BDMC33 abolished the p65 NF-kB nuclear translocation and NF-kB DNA binding activity in PMA-stimulated SF.

Conclusion & Significance: BDMC33 represents an effective chemopreventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention.

Key words: BDMC33, curcumin, HIG-82, matrix metalloproteinase, NF-kB, synovial fibroblast.