Tamoxifen decreases fibroblast function and downregulates TGF(beta2) in dupuytren's affected palmar fascia.
BACKGROUND
Dupuytren's contracture is a fibroproliferative disorder that is associated with increased collagen deposition. Isoforms of transforming growth factor beta (TGF(beta)), normally TGF(beta1) and TGF(beta2), are involved in the progressive fibrosis of Dupuytren's disease. It has been suggested that downregulation of TGF(beta) may be useful in the treatment of the condition. Tamoxifen, a synthetic nonsteroidal antiestrogen, is known to modulate the production of TGF(beta). This study examined the role of tamoxifen in decreasing fibroblast function and downregulating TGF(beta2).


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 TGF(beta2) 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 TGF(beta2) expression in the Dupuytren's affected fascia group compared to the carpal tunnel control group. Tamoxifen decreased TGF(beta2) expression in Dupuytren's affected fascia group but not in the carpal tunnel control group.


CONCLUSIONS
TGF(beta) 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 TGF(beta2) production in these same fibroblasts. These data suggest a method to manipulate and control Dupuytren's contracture in the clinical setting.
Kuhn
M Ann
MA
Department of Veterans Affairs Medical Center, Institute of Tissue Regeneration, Repair, and Rehabilitation, Bay Pines, Florida 33744, USA.
Wang
X
X
Payne
Wyatt G
WG
Ko
Francis
F
Robson
Martin C
MC
D002349:Carpal Tunnel Syndrome / Q000473:pathology; D018929:Cell Culture Techniques; D003094:Collagen; D004387:Dupuytren Contracture / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005205:Fascia / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053781:Transforming Growth Factor beta2
D004965:Estrogen Antagonists; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D013629:Tamoxifen; D003094:Collagen