Cellular structure and biology of Dupuytren's disease.
Numerous studies support the idea that the myofibroblast is a key cell responsible for the tissue contraction in Dupuytren's disease. In vitro models have been developed to study the underlying cellular basis of myofibroblast differentiation and contraction. Studies suggest that the growth factor TGF-beta 1 combined with mechanical stress can promote the differentiation of fibroblasts into myofibroblasts. Agonists, such as LPA and thrombin, can promote the contraction of myofibroblasts through specific intracellular signaling pathways that regulate levels of phosphorylated myosin light chain. Agents that can affect these intracellular signaling pathways hold promise as a means to decrease contraction of the myofibroblast and of the palmar fascia in Dupuytren's disease. Finally, the recent finding that IFN-gamma can suppress both the differentiation of the myofibroblast and the generation of contractile force, together with preliminary clinical results using IFN-gamma, suggest the potential use of IFN-gamma for nonsurgical therapy of Dupuytren's disease. Future studies into the cellular basis of tissue contraction should provide alternative methods to improve management of Dupuytren's contracture.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
J J
JJ
Tomasek
M B
MB
Vaughan
C J
CJ
Haaksma
D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004387:Dupuytren Contracture / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005347:Fibroblasts / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology
D003598:Cytoskeletal Proteins; D005353:Fibronectins