Dupuytren's cells used in another scientific paper

Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture: 

BMC Med Genomics. 2012; 5: 15.Published online 2012 May 4. doi:  10.1186/1755-8794-5-15

PMCID: PMC3375203

The introduction to this paper starts with the normal spiel about the things associated with this disease and I didn't really learn anything new there. There was also the usual talk about it coming back and this again is of unknown cause but likely because of genetics or sufficient disease tissue being left behind to cause regrowth. 

In this paper they are looking at cells from Dupuytren's and carpel tunnel patients as well as normal uninvolved tissue to use as a comparison. For those with limited understanding of science or those that fancy a refresh have a quick look at this post  -- Analysis of Duputren's cells -- I will try and explain the science here but reading the previous post will probably help. 

In this paper they are using a technique that is called a micro-array this allows them compare the levels of thousands of different read outs from the different types of cells are compare them. This means that if they have 4 different cells lines (i.e. 4 different groups of cells derived from different patients) they can build up a profile of what the cells from patients with this condition look like and see how they are the same and how they are different from 'normal' cells. This is a big deal for something like Dupuytren's where of course they do not know what the cause is, they have some idea of the pathways involved 

• Can scar formation be used as a useful model for Ledderhose and Dupuytren's?

• IGF-2 and its relationship to Dupuytren's

The advantage of a micro-array is that it allows you to look at allow the changes that are happening in all the pathways in the cells that have come directly from patients. 

The Results:

I will stick to looking at what they found for the Dupuytren's tissue rather than bog down the post with the carpel tunnel stuff, When comparing DC and normal cells they found out that there were 308 transcripts that were different between the two cell types, they also show lots of other data saying that there is some difference between the two different sets of cells. 

They next go on to look at identification of biological pathways that are altered among these different cell types. When looking at the pathways altered in the different cell types for Dupuytren's and normal cells were related to cell death, cell growth and proliferation (speed and control of growth) which of course makes sense when you see less cell death and too much cell growth and division in Dupuytren's cells. The analysis also suggested that there was some involvement of the regulation of things called microRNAs. These results were then validated using another technique which showed that the results were reliable. 

They conclude by saying that the progression and recurrence of DC could be based upon similar theories to those applied to tumour biology (in no way are they suggesting it is cancerous). They say that perhaps there is an inherited mutation but that it takes a second mutation to cause the disease to become active, this kind of fits with the fact that the disease appears to be dominant but with a variable hit rate as the dominant factor is the initial mutation but the variable bit is acquiring the second one. Again this also fits with the disease normally happening later in life as this would give time for the additional mutation to occur.  

They have a lot more information in that paper which is why I have linked to it above. Hopefully research continues into these conditions so that a better and more successful treatment / cure can be found. 

Analysis of Dupuytren's Cells

So I thought it was about time for another science post, don't worry it is only going to be a short one and is again based on a chapter from the book, Dupuytren's Disease and Hyperproliferative Disorders. C. Eaton et al, Chapter 14.

Right so for those who don't know (I have explained it before but hey and see the picture below from the previous post) DNA is a constant in the cell and it is converted to mRNA in a regulated manner which is then converted into proteins which have an effect.

The central dogma 

So one way of analysing cells and differences in them is to look at the levels of mRNA. There is a technique called a Microarray and whilst I will not going into detail here what it basically does is give you a read out of the levels of mRNA for pretty much every gene, so what that means is that you have a read out of how much there is of the things that are responsible for what happens in the cell.

So what they have decided to do in this experiment is to get cells from patients with Dupuytren's disease from healthy and Dupuytren's tissue and they look at what differences there are between the 2 different types of cells using a microarray. This is then repeated, in this case on 20 patients and they look at what mRNAs are at different levels in ALL patients and from this they come up with a list of genes (genes are the DNA that codes for the mRNA) that might be linked to Dupuytren's disease.

They then cut this already small list down to ones that are likely to play a role in the development of Dupuytren's and in particular they are looking at the ones that are likely to play a role in contracture. They come up with several different proteins which I won't go into as they don't mean anything to me but they come up with things that are involved with the extracellular matrix (ECM) which plays an important role in connective tissue and I have mentioned it in my past post along with collagen.

They then go on to basically say that there are some mRNAs that are at a lower level in the disease tissue and this might be linked to the development of contracture but do not speculate as to how and how this might be useful. I guess knowing the cause if the first step towards a sure and this information helps in the understanding of the cause.