ABSTRACT
Dupuytren's disease (DD) is a superficial fibromatosis of the hand. Although the molecular mechanisms responsible for this disease are unknown, recent studies suggest that beta-catenin may be a key factor involved in fibromatosis. In this study, we analysed the in vivo and in vitro expression levels of beta-catenin in DD, using surgical specimens and primary cell lines. Although no somatic mutations (exon 3) of beta-catenin were detected, Western blot analysis revealed high levels of beta-catenin in diseased palmar fascia, and low to undetectable levels of beta-catenin in patient-matched normal palmar fascia. Immunohistochemistry analysis showed high levels of beta-catenin expression within the disease fascia, as well as cytoplasmic and nuclear accumulations of the protein. Immunoprecipitation of beta-catenin from seven patient lesions showed the protein to be tyrosine phosphorylated. Lastly, Western analysis of three patient-matched (disease and normal fascia) primary cell cultures showed significantly elevated levels of beta-catenin in disease cells cultured in three-dimensional collagen lattices. This is the first extensive in vivo and in vitro characterization of beta-catenin in DD, and the first to suggest that the extracellular matrix may play an important role in modulating beta-catenin stability in DD.
Subject(s)
Cytoskeletal Proteins/analysis , Dupuytren Contracture/metabolism , Extracellular Matrix/physiology , Trans-Activators/analysis , Blotting, Western , Humans , Immunohistochemistry , Mutation , Phosphorylation , Tyrosine , beta CateninABSTRACT
The first author to suggest an origin and spread of Dupuytren's disease was Early who wrote in 1962, "If one postulates the condition as having arisen in one particular racial group (the Nordic for example) then the variable distribution in other parts of the world might be explained on the basis of migration from that group." Dupuytren's disease is currently called a Viking disease on the assumption that the disease was spread to Europe and the British Isles during the Viking Age of the 9th to the 13th centuries. From a literature search, it is proposed that Dupuytren's disease existed in Europe earlier than the Viking Age and originated much earlier in prehistory.
Subject(s)
Dupuytren Contracture/history , Dupuytren Contracture/genetics , Emigration and Immigration , Genetics, Population/history , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, Ancient , History, Medieval , HumansABSTRACT
The extensor tendons to the index, long, ring and small fingers are motored by the common extensor digitorum communis muscle body. Effective function of this muscle can only occur if the gliding amplitude of each of its four extensor tendons is normal. As a corollary, limitation of the excursion of any of the individual tendons by adhesions at a fracture or tendon repair site, a fixed flexion contracture at the metacarpophalangeal joint, or by rupture, attenuation or laceration of a saggital band or juncturae tendinum, will result in reduction of the excursion of the adjacent extensor tendons. This pathological state has been termed the extensor quadriga because of its similarities to the analogous pathology affecting the flexor digitorum profundus system. Improper management of this clinical entity may lead to an abnormal pathomechanical kinematic chain imbalance. Early identification and treatment is critical to address this entity appropriately.
Les tendons extenseurs de l'index, du majeur, de l'annulaire et de l'auriculaire sont mus par le muscle extenseur commun des doigts. Mais celuici ne peut fonctionner adéquatement que si l'amplitude de glissement de chacun des quatre tendons extenseurs est normale. En corollaire, une restriction de mouvement de l'un ou l'autre des quatre tendons, due à des adhérences en un foyer de fracture ou au siège de réparation d'un tendon, à une contracture fixe en flexion à une articulation métacarpo-phalangienne ou encore à une rupture, à une faiblesse ou à une lacération d'un ligament sagittal ou du tendon commun, entraîne une restriction de mouvement des tendons extenseurs adjacents. On a donné à ce syndrome le nom de « quadrige des extenseurs ¼ en raison de ses ressemblances avec un syndrome analogue qui touche le muscle fléchisseur commun profond des doigts. Un traitement inapproprié de ce trouble clinique peut conduire à un déséquilibre de la chaîne cinématique pathomécanique. Aussi est-il crucial de reconnaître et de traiter précocement ce syndrome afin d'en assurer une prise en charge adéquate.