The exact process is still unknown, despite many bits of information. The body chemistry is abnormal in the entire region, even in areas not visibly changed by Dupuytren’s 3373152, 6768572, 589933, 9369955, 8501391. Here are a few parts of the picture – see if you can figure out how all of this fits together…
- The balance between certain enzymes (matrix metalloproteinases 14504511, 9768907, fibrinolysins 3958550, plasminogen activators 3693826) and their natural inhibitors is disturbed in patients with active Dupuytren’s disease, and may be affected by tension on the affected tissues 9665512.
- The cells in the cords of Dupuytren’s disease are unusually sensitive to the effects of “growth factors”, normal body chemicals involved in wound healing. These include transforming growth factor beta 1 (TGF-beta(1) 12849947, 12729127 ,8618012, transforming growth factor beta 2 (TGF-beta(2) 12678125, 8683048, basic fibroblast growth factor (bFGF)1325742, platelet derived growth factor (PDGF) 12087679, 7822340, 1564283 and others 9120728, 7722248, 8056971,8320323. The process may be triggered by a combination of mechanical stress and either TGF-beta 10050239, or PDGF8893764 .
- Dupuytren’s cords have unusually high levels of levels of the protein tyrosine phosphorylated beta-catenin 12802275 , and the cells have higher than normal levels of the substance alpha smooth muscle actin 11599921 and the enzyme lysyl oxydase 6130030.
- Cell-matrix interaction abnormalities, stimulating contraction 9369955, 9065582, 8525780. A three dimensional mesh of actin microfilaments (the “fibronexus”) links cells to each other and to the extracellular matrix 1867394, which, in Dupuytren’s disease, contains unusually high levels of fibronectin 3519746, 6386626.
- Abnormal androgen receptors have been implicated in the abnormal tissue 11853085 , 10194020, 1798252, although not by all investigators 3794501.
- Low oxygen levels resulting in reactive forms of oxygen (superoxide free radicals, oxygen free radicals) due to poor circulation have been implicated 12087679, 10050241, 1769989, possibly due to activation of the enzyme xanthine oxidase1695516, 2825907. The blood clotting system may be triggered by production of high level of plasminogen activator6197420. Microvascular circulatory changes develop, with narrowing and blockage of capillaries 1960491, 2322211,2722922, microscopic hemorrhage 6693745 and other changes in the blood vessel walls 4082789, 6150573. This might explain the relationship of smoking to Dupuytren’s. Miroculatory changes may arise from abnormal regulatory nerves in the fascia itself 2472714. Nodules show near complete absence of blood vessels 6693745, and other studies show evidence of low oxygen levels in the diseased tissues 6877040.
- T-cell and B-cell Immune mechanisms , 9888668, 8099992, autoantibodies to collagen 8181183, 3485693 or other immune mechanisms 2471021, 3138883, 6353806 may be involved.
- Genetic variations have been demonstrated in nodules, in the form of recurrent clonal numerical abnormalities 9973941,9352799,3414684.
- The contraction is due to a mechanism also seen in other contracting tissues such as healing wounds and some types of cancers 6491814. Dupuytren’s fibroblasts 6507097 can acquire smooth muscle characteristics and are then able to contract 7642925. These modified fibroblasts are called myofibroblasts 1960491, and are found in nodules, but not cords1769990, 6491814, 7071229. In diffuse disease, these changes can affect cells in the skin as well as the fascia 8294839. Myofibroblasts contract through an interaction of myofilaments and the enzyme ATPase within their cell bodies, and the extent of recurrence after surgery correlates with myofibroblast activity at the time of surgery 6683733, 2754197.
- Certain nerve endings (Pacinian corpuscles) are enlarged and surrounded by fibrous tissue in affected areas 3358315,2472714.
- Overall collagen metabolism may be disturbed in patients with Dupuytren’s 2883783. Type III collagen is increased in Dupuytren’s cords 6386626, 6740656.
- Mechanical tension forces or stretching the affected area may provoke contracture 14599823, 12866952, 12449347,10050239, 9763277, 9665511, possibly by stimulating changes in the microcirculation 8917718. Dynamic physical forces may produce biochemical changes through changes in tissue electrical fields 1284015 . Paradoxically, continuous tension on the tissues causes a temporary reversal of the process, probably by stimulating enzymes involved in tissue remodelling7964107. One hypothesis is that loss of normal gliding motion between layers of fascia results in abnormal tissue tension which provokes the contracture process 7152372.