文本框: STIMULATION OF SYNOVIAL CELL GROWTH AND EXPRESSION OF c-myc PROTOONCOGENE BY IRON AND REVERSAL BY CERAMIDE: IMPLICATIONS FOR HEMOPHILIC SYNOVITIS 1Wen F-Q, 1Chen Y-X, 2Jabbar A, 2Kazarian T, 2Valentino LA. 1Department of Pediatrics, Second Affliliated Hospital, Jinan Medical College, Jinan University, Shenzhen, China 2Department of Pediatrics and Immunology/Microbiology, Rush Children’s Hospital and Rush University, Chicago, Illinois, USA Objectives: To test the hypothesis that iron, present in the blood, stimulates synovial cell proliferation as a result of aberrant expression of proto-oncogene c-myc. Methods: CellTiter 96Aqueous non-radioactive cell proliferation assay kit was used to determined the rate of human synovial cell growth, c-myc gene expression of the cells was assayed by RT-PCR and flurescent microscopic apoptosis assay was used to detect apoptosis in the synovial cells. Results: Normal human synovial cells exposed to iron salt (Fe-citrate, 0.1 and 1.0 mM) for nine days experience a more than 50% increase in cell growth compared to control cells (Na-citrate) (OD450 0.17±0.023 vs 0.10±0.013 and 0.19±0.013 vs 0.12±0.009 respectively)(p<0.001). The expression of c-myc was enhenced in cells exposed to the both concentrations of iron compared to control cells (Na-citrate). Treating the iron-exposed cells with ceramide (C2-ceramide, 25 or 50 μM), a chemical mediator of apoptosis, reversed the increase in cell proliferation, increased apoptosis of the cells and prevented the increase in c-myc expression. Conclusion: (1) Iron stimulates the proliferation of human synovial cell (2) Iron upregulates the proto-oncogene c-myc. (3) Ceramide abrogates the iron-induced increase in synovial cell proliferation and upregulation of c-myc. (4) Ceramide may be a useful therapeutic tool to treat hemophilic synovitis. 0694