RNA, Growth Factors and Dupuytren's

Sorting out the genetic basis of Dupuytren's is not simply a matter of finding out which genes are involved. The goal is to understand the biochemistry of exactly what these specific genes do to either start or fail to stop the process of Dupuytren's. Cell biology is always a domino like set of events with many steps. The DNA molecules in a cell's genes act as a template to make messenger RNA (mRNA), which travels from the cell's nucleus to its protein manufacturing factories (ribosomes), where the mRNA then acts as a template to string amino acids together to make proteins. Our bodies use some proteins, like collagen, as structural building material; other proteins, called cytokines, are used as currency of communication between cells, directing cells what to do. In this study, "Abnormal growth factor and cytokine expression in Dupuytren's contracture" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1993_Baird_1442.pdf), researchers analyzed the cytokines produced by mRNA in Dupuytren's tissue, and found abnormal activity of interleukin-1a, interleukin-1ß, transforming growth factor ß and basic fibroblast growth factor. This approach, linking genes with proteins, brings us a step closer to solving the puzzle of a cure.

ß Catenin, Transforming Factor ß and Dupuytren's

The physical changes associated with Dupuytren's are similar to the process which heals open wounds through contraction and collagen production. Thanks to sophisticated laboratory research, the molecular controls for this process are beginning to be understood. See http://multimedia.mcb.harvard.edu/anim_innerlife.html for an amazing animation of how molecular cellular controls act like tiny physical machines. In Dupuytren's, two controls are ß Catenin and Transforming Factor ß. ß-catenin is a protein which is part of the physical scaffolding in a cell. Among many functions, ß-catenin forms part of a cellular trailer hitch which locks one cell to the next, called the adherens junctions (AJs). Transforming Factor ß is a protein which is produced by some cells to activate receptors on other cells, part of the autocrine system of cell signaling. It has different effects in different situations. Both ß Catenin and Transforming Factor ß are major players in Dupuytren's type tissue contracture. How do they interact with each other? Somewhat independently, according to this study (full text http://www.dupuytrenfoundation.org/DupPDFs/2009_Poon.pdf). ß Catenin primarily activated cell migration while Transforming Factor ß mainly stimulated cell growth and contraction, which would seem to be the more important process in Dupuytren's. Interesting, but more details are needed to crack the code to find a cure.