Cytokine manipulation of explanted Dupuytren's affected human palmar fascia.
BACKGROUND
Dupuytren's disease plagues human hands and digits producing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. Interest in this condition is great but because the disease is specific to humans and study has been hampered by the lack of an in vivo model. By utilizing an in vivo "nude" rat model it is possible to maintain and study explanted Dupuytren's contracted palmar fascia for prolonged periods of time.


METHODS
Human specimens were divided into four, one for in vitro analysis, and three for model explantation. The explanted tissue was perfused with either transforming growth factor beta-2 (TGFbeta2), its antibody, or a control vehicle. Explant biopsies were obtained at 30 and 60 days and compared to tissue prior to explantation. Immunohistochemistry of collagen I and III, DNA synthesis, protein production, and fibroblast kinetics were serially determined.


RESULTS
Perfusion of explanted Dupuytren's tissue by TGFbeta2 upregulated collagen I and III from biopsies obtained from the explants at 30 days when compared to vehicle control (P < 0.001). Perfusion with antibody prevented this upregulation when compared to vehicle control (P < 0.001). Cell cultures derived from fibroblasts obtained from biopsies of the explants perfused with TGFbeta2 increased DNA synthesis, protein production and fibroblast kinetics.


CONCLUSIONS
These findings paralleled those from other fibroproliferative disorders suggesting a role for TGFbeta2 in the pathogenesis of Dupuytren's contracture as well as possible novel treatment approaches.
Kuhn
M A
MA
Institute of Tissue Regeneration Repair and Rehabilitation, Department of Veterans Affairs Medical Center, Bay Pines, FL 33744, USA.
Payne
W G
WG
Kierney
P C
PC
Pu
L L
LL
Smith
P D
PD
Siegler
K
K
Ko
F
F
Wang
X
X
Robson
M C
MC
D000704:Analysis of Variance; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004387:Dupuytren Contracture / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D005205:Fascia / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013524:Surgical Flaps; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2
D016207:Cytokines; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2