Matrix and cell phenotype differences in Dupuytren’s disease

Abstract

BackgroundDupuytren’s disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient. The disease first causes a nodule in the palm of the hand, while later, a cord develops, causing contracture of the fingers.ResultsWe set out to characterize the two phenotypes by comparing matched cord and nodule tissue from ten Dupuytren’s patients. We found that nodule tissue contained more proliferating cells, CD68-positive macrophages and α-smooth muscle actin (α-SMA)-positive myofibroblastic cells. qPCR analysis showed an increased expression of COL1A1, COL1A2, COL5A1, and COL6A1 in nodule tissue compared to cord tissue. Immunohistochemistry showed less deposition of collagen type I in nodules, although they contained more fibronectin, collagen type V, and procollagen 1. Lower collagen levels in nodule were confirmed by HPLC measurements of the Hyp/Pro ratio. PCOLCE2, an activator of BMP1, the main enzyme cleaving the C-terminal pro-peptide from procollagen, was also reduced in nodule. Cord tissue not only contained more collagen I, but also higher levels of hydroxylysylpyridinoline and lysylpyridinoline residues per triple helix, indicating more crosslinks.ConclusionsOur results clearly show that in Dupuytren’s disease, the nodule is the active disease unit, although it does not have the highest collagen protein levels. The difference in collagen type I deposition compared to mRNA levels and procollagen 1 levels may be connected to a decrease in procollagen processing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13069-016-0046-0) contains supplementary material, which is available to authorized users.

Glimpses into the molecular pathogenesis of Peyronie’s disease

“…We found an increased expression of Wnt4, b-catenin and YAP1 in plaques, and observed changes related to collagen quantity and quality. Part of our findings coincide with recent observations in DD [27][28][29], underscoring a certain relationship between both disease states. We obtained plaque and unaffected tissue from the tunica albuginea of the same patient, and by doing so, we excluded inter-individual variations.…”

“…As the main constituents in fibrotic tissues are collagen and fibronectin, the decreased expression of fibronectin will contribute to a different composition of the extracellular matrix in plaque. Differences in fibronectin mRNA expression have also been observed between the cord and the nodule in DD [29], whereas no differences were seen in mRNA levels among elastin, decorin, biglycan, and fibromodulin, which is similar to what we observed in PD.…”

Mechanical and migratory properties of normal, scar, and Dupuytren's fibroblasts

“…Dupuytren's disease is a fibromatosis of the connective tissue of the palm that can lead in certain cases to the immobility of one or more fingers due to formation of nodules and cords in the palmar fascia . Connective tissue represents the architectural and supportive framework of many tissue and organs in animal body, and it is mainly composed by fibroblasts.…”

Active synthesis of type I collagen homotrimer in Dupuytren’s fibrosis is unaffected by anti-TNF-α treatment

“…but not COL1A2 mRNA in Dupuytren's tissue, as compared to shoulder capsule (Kilian et al, 2007). In the present study, we did not distinguish between nodule and cord for RNA analysis, although a prior study found both COL1A1 and COL1A2 mRNA was higher in nodule as compared to cord, despite lower collagen (I) protein being present in nodule (van Beuge et al, 2016).…”