Effect of telomerase on proliferation and differentiation of a cell line derived from Dupuytren's contracture

Abstract

Dupuytren's disease is a fibroproliferative disorder that affects the hand's palm and eventually leads to loss of hand function. It is characterized by shortening of the palmar fascia and an increased myofibroblast percentage excised from Dupuytren's contracture surgery. Transforming growth factor-beta enhances the formation of structural elements and elevated expression of alpha-smooth muscle actin in myofibroblasts. The objective of this study was to determine the ability of the immortalized myofibroblast to differentiate as expected in response to transforming growth factor-beta to provide unlimited supply to investigate further the causes and treatments for Dupuytren's disease. A 3-dimensional collagen lattice was used to study tension generation and contraction using an immortalized cell line derived from Dupuytren's disease (DP147+hTERT). In addition, it was compared to its parental cell line derived from Dupuytren's contracture (DP147). We determined tension generation and contraction by measuring the decrease in the surface area of the collagen lattice over time for both cell line types. It was followed by immunostaining to calculate the percentage of myofibroblasts and proliferation. In addition, cells were plated on coverslips then immunostained to determine differences in differentiation and proliferation between DP147 and DP147+hTERT. The results were encouraging for using the immortalized cell line for future studies on Dupuytren's disease; both cell lines showed increased myofibroblast differentiation in response to TGF-beta. Still, further investigations are required to understand differences in proliferation between DP147 and DP147+hTERT and its effect on the reliability of the immortalized cell line.