Disease Of Palmar Fascia Research Articles

Vitamin D status in Dupuytren's disease: Association with clinical status and vitamin D receptor expression

Dupuytren's disease (DD) is a progressive fibroproliferative condition involving contractures of the fascia of the palm. Up to now, there are no relevant investigations on patients with DD in case of serum vitamin D deficiency. We hypothesized that transforming growth factor-β1 (TGF-β1) is increased in patients with DD in consequence of vitamin D deficiency, thereby leading to myofibroblast differentiation and subsequent progression of contractures. The aim of this study was to analyze serum vitamin D levels and explore possible clinical and immunohistochemical correlates with vitamin D concentrations in a group of patients with DD. Vitamin D levels were measured in all patients with DD and healthy controls. In the patient group, clinical characteristics were compared between vitamin D deficient and nondeficient subgroups. Diseased palmar fascia samples were obtained from 14 patients undergoing fasciectomy for DD. Correlations between vitamin D levels and vitamin D receptor(VDR), TGF-β1 expression levels in collected fascia samples were evaluated. Vitamin D concentrations were significantly lower in patients than in healthy controls. In addition, total extension deficit of involved fingers was higher in vitamin D deficient patients. Moreover, a positive correlation was found between vitamin D levels and expression of VDR in pathologic fascia in patients undergoing fasciectomy for contracture. Serum vitamin D levels were found to be low in patients with DD. Expression of VDR was lower in the vitamin D deficient group. The results suggest a potential link between vitamin D status and DD but causation is not yet established. The potential role of vitamin D and its interaction with VDR and the TGF-β1 signaling pathway in the pathogenesis of DD needs to be explored further.

3-Dimensional fasciectomy: A highly efficacious common ground approach to Dupuytren's surgery.

BackgroundNumerous Dupuytren’s fasciectomy techniques have been described, each associated with unique surgical challenges, complications and recurrence rates. We describe a common ground surgical approach to Dupuytren’s disease; 3-dimensional fasciectomy (3DF). 3DF aims to address the potential contributors to the high recurrence rate of Dupuytren’s disease and unite current limited fasciectomy practice that varies considerably between surgeons.MethodsWe describe the 3DF principles; raising thin skin flaps (addressing dermal involvement), excising diseased palmar fascia with a 3−5 mm clearance margin (treating highly locally recurrent conditions) and excising the vertical septae of Legueu and Juvara (providing deep clearance, hence addressing all potentially involved pathological tissue). The surgical outcomes between traditional limited fasciectomy (LF) and 3DF are compared.ResultsFrom the 786 operations included (n=585), postoperative recurrence rates were significantly lower for the 3DF group (2/145, 1.4%) than the LF group (72/641, 11.2%) (P=0.001), and the time to recurrence was significantly longer (5.0±0 years vs. 4.0±0.2 years; P<0.0001). With recurrence excluded, there were no differences between the postoperative complication rates for 3DF (5/145, 3.5%) and LF (41/641, 6.4%) (P=0.4).ConclusionsOur results suggest that 3DF leads to lower recurrence rates and a longer disease-free period for patients, without increasing complications. 3DF provides a safe, efficacious, common ground surgical approach in the treatment of Dupuytren’s flexion deformity.

The role of skin and subcutaneous tissues in Dupuytren's contracture: an electron microscopic observation

To determine the relationship between the overlying tissues and recurrence of Dupuytren's contracture. Forty-three patients (68 hands) who accepted surgical treatment were divided into two groups according to treatment methods: partial fasciectomy or dermofasciectomy and full-thickness skin graft. Diseased palmar fascia, subcutaneous tissues and skin obtained during surgery were then assessed by electron microscopy. All patients were followed up. None of the hands which accepted dermofasciectomy and full-thickness skin grafting recurred, while 46.4% of the hands which accepted partial fasciectomy recurred. Under electron microscopic observation, myofibroblasts were found in the skin and subcutaneous tissues. The overlying tissues play an important role in Dupuytren's contracture, which may be a reason for recurrence of this condition after surgical treatment.

Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture

Dupuytren's contracture (DC) is the most common inherited connective tissue disease of humans and is hypothesized to be associated with aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts are believed to play an important role in the genesis of DC and the fibroproliferation and contraction that are hallmarks of this disease. This study compares the gene expression profiles of fibroblasts isolated from DC patients and controls in an attempt to identify key genes whose regulation might be significantly altered in fibroblasts found within the palmar fascia of Dupuytren's patients. Total RNA isolated from diseased palmar fascia (DC) and normal palmar fascia (obtained during carpal tunnel release; 6 samples per group) was subjected to quantitative analyses using two different microarray platforms (GE Code Link™ and Illumina™) to identify and validate differentially expressed genes. The data obtained was analyzed using The Significance Analysis of Microarrays (SAM) software through which we identified 69 and 40 differentially regulated gene transcripts using the CodeLink™ and Illumina™ platforms, respectively. The CodeLink™ platform identified 18 upregulated and 51 downregulated genes. Using the Illumina™ platform, 40 genes were identified as downregulated, eleven of which were identified by both platforms. Quantitative RT-PCR confirmed the downregulation of three high-interest candidate genes which are all components of the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1) transcript variant D, and type XV collagen alpha 1 chain. Overall, our study has identified a variety of candidate genes that may be involved in the pathophysiology of Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies.

Beta-catenin expression in Dupuytren's disease: potential role for cell-matrix interactions in modulating beta-catenin levels in vivo and in vitro.

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.

Pharmacologic regulation of Dupuytren's fibroblast contraction in vitro

Dupuytren's disease is associated with contraction of specialized fibroblasts present in the diseased palmar fascia. Pharmacologic agents were evaluated for their ability to promote or inhibit contraction of Dupuytren's fibroblasts in vitro using a collagen lattice contraction assay. In the first part of the study, lysophosphatidic acid (LPA), serotonin, angiotensin II, and prostaglandin F2 alpha were tested for their ability to promote Dupuytren's fibroblast contraction. Lysophosphatidic acid was found to significantly promote Dupuytren's fibroblast contraction as compared with controls. This response to LPA is dose dependent, with a half-maximal response of 0.07 microM. Angiotensin II, serotonin, and prostaglandin F2 alpha at 1 mM, induced a significant amount of contraction as compared to controls, but the amount of contraction was at least six times less than that observed for LPA. In the second part of the study, prostaglandins E1 and E2 or the calcium blockers nifedipine and verapamil were tested for their ability to inhibit LPA-promoted contraction. It was found that both types of inhibitors partially block LPA-promoted contraction of Dupuytren's fibroblasts. The effect of the various pharmacologic agents on normal palmar fibroblasts was not evaluated. The focus of this study was to examine the regulation of contraction of Dupuytren's fibroblasts. This study demonstrates that LPA is a potent agonist of Dupuytren's fibroblast contraction and that this contraction can be inhibited by specific pharmacologic agents. These findings provide a rational basis for investigating further the clinical use of the calcium channel blockers nifedipine or verapamil and prostaglandins E1 and E2 to control Dupuytren's disease and possibly other fibrotic conditions.

Distribution of ED-A and ED-B containing fibronectin isoforms in dupuytren's disease

Different fibronectin (FN) isoforms arise via alternate splicing of a single gene transcript in a cell- and tissue-specific manner. Antibodies were used to evaluate the presence and distribution of FN and its isoforms in Dupuytren's diseased and normal palmar fascia. Immunolocalization studies show extracellular FN fibrils, including FN isoforms containing extra domains A (A-FN) and B (B-FN), in proliferative and involutional stage Dupuytren's diseased tissue. However, B-FN appears less abundant and more restricted in its distribution as compared to A-FN or total FN. Total FN and A-FN are significantly reduced in residual tissue, while B-FN is not present. A-FN and B-FN are not present in normal palmar fascia, while total FN staining is slight and restricted to the loose connective tissue surrounding the large, parallel bundles of collagen fibers. The presence of A-FN and B-FN in Dupuytren's diseased palmar fascia represents a disease-induced appearance of these FN isoforms and further evidence of an association between Dupuytren's disease and wound healing.

Oestrogen and progesterone hormone receptors in Dupuytren's disease

Dupuytren's disease is associated with alcoholism and chronic liver disease, conditions frequently associated with deranged steroid hormone metabolism. The possible influence of endogenous sex steroid hormones on the development of Dupuytren's disease has therefore been investigated. An analysis of diseased palmar fascia for oestrogen and progesterone receptors was undertaken in fifteen patients. Hormone specific receptors were not found in the palmar fascia of our patients with Dupuytren's disease, thus suggesting that other mechanisms or factors contribute to the pathogenesis of this fibrotic process.

Oestrogen and Progesterone Hormone Receptors in Dupuytren’s Disease

Dupuytren’s disease is associated with alcoholism and chronic liver disease, conditions frequently associated with deranged steroid hormone metabolism. The possible influence of endogenous sex steroid hormones on the development of Dupuytren’s disease has therefore been investigated. An analysis of diseased palmar fascia for oestrogen and progesterone receptors was undertaken in fifteen patients. Hormone specific receptors were not found in the palmar fascia of our patients with Dupuytren’s disease, thus suggesting that other mechanisms or factors contribute to the pathogenesis of this fibrotic process.

The cytoskeleton and extracellular matrix of the Dupuytren's disease “myofibroblast”: An immunofluorescence study of a nonmuscle cell type

The cytoskeleton and the extracellular matrix of myofibroblasts in nodules from Dupuytren's diseased palmar fascia were examined by indirect immunofluorescence. Primary antibodies used as probes of these tissue compartments were directed against (1) smooth muscle myosin, (2) nonmuscle myosin--components of the cytoplasmic contractile apparatus in smooth muscle and nonmuscle cells, respectively, (3) laminin, and (4) fibronectin--extracellular glycoproteins mediating cell-matrix attachment in smooth muscle and nonmuscle fibroblastic cells, respectively. The Dupuytren's nodular cells stained for nonmuscle myosin and fibronectin but not for smooth muscle myosin or laminin; this indicated that, at the level of biochemical differentiation, these cells are a nonmuscle type. Staining for fibronectin between nodular cells was dramatically increased over that seen between fibroblasts of the normal palmar fascia. Because of the non-muscle nature of the distinctive contractile cell type of the Dupuytren's nodule, we suggest that the term myofibroblast should be considered a misnomer when applied to this pathogenic cell type.