Tamoxifen Decreases Fibroblast Function and Downregulates TGFβ2 in Dupuytren's Affected Palmar Fascia

Abstract

Background. Dupuytren's contracture is a fibroproliferative disorder that is associated with increased collagen deposition. Isoforms of transforming growth factor beta (TGFβ), normally TGFβ1 and TGFβ2, are involved in the progressive fibrosis of Dupuytren's disease. It has been suggested that downregulation of TGFβ may be useful in the treatment of the condition. Tamoxifen, a synthetic nonsteroidal antiestrogen, is known to modulate the production of TGFβ. This study examined the role of tamoxifen in decreasing fibroblast function and downregulating TGFβ2.Methods. Primary cultures of fibroblasts were obtained from Dupuytren's affected fascia and carpal tunnel affected fascia as a control. Collagen lattices were prepared and populated with the fibroblasts. The fibroblast-populated collagen lattices (FPCL) were then measured for contraction every 24 h for 5 days. Supernatant was obtained from the culture medium following completion of the FPCL portion of the experiment and used for a TGFβ2 immunoassay.Results. Dupuytren's affected fibroblasts contracted the FPCLs significantly more than carpal tunnel control fibroblasts. Treating the fibroblasts with tamoxifen caused a decreased contraction rate in both Dupuytren's affected fibroblasts and carpal tunnel controls. There was increased TGFβ2 expression in the Dupuytren's affected fascia group compared to the carpal tunnel control group. Tamoxifen decreased TGFβ2 expression in Dupuytren's affected fascia group but not in the carpal tunnel control group.Conclusion. TGFβ appears to be the key cytokine in the fibrogenic nature of Dupuytren's disease. Tamoxifen treatment has been demonstrated to decrease the function of fibroblasts derived from Dupuytren's affected fascia and downregulated TGFβ2 production in these same fibroblasts. These data suggest a method to manipulate and control Dupuytren's contracture in the clinical setting.