Tuesday, 6 March 2012
Can scar formation be used as a useful model for Ledderhose and Dupuytren's?
So today my foot was hurting from about 11am onwards which is a new early start record for me, yey. Consistent with this when I had to walk for 5 minutes my foot was really hurting, I was limping quite bad and grimacing and all that malarkey but luckily today I managed to get a spot on the train and the bus. The pain however was bad enough that I thought I should look into seeing about getting a folding walking stick, that way I can have it on me and use it when I need to take the pressure off of my foot, sure it is not ideal and I will have to get over the sense of annoyance and to some extent embarrassment at having to use one but if I need to that I need to.... still bet I couldn't get a disabled badge for the car even though you see people using those spaces all of the time and there are always people on yellow lines that think it is ok because the other car did it when the other car actually had a disabled badge.
Onto the scar formation thing that I wanted to talk about today. Must say that I am going to be really naughty and use wikipedia as a source of information, this is really bad but the page seems to be well sourced so I don't feel too bad using it.
Introduction to scars and why they are important in understanding Dupuytren's disease (DD) and Ledderhose Disease (LD):
So basically the reason for this post is, as many of you will know, that the formation of DD and LD nodules is thought (in some cases at least) to be caused by an over response to trauma and is essential scar tissue and this is why when you cut it away it often comes back as surgery gives it plenty of scar tissue to initiate from. So of course if it can be understood how normal scar tissue is formed and regulated and indeed how we can stop the formation of scar tissue in cases where it is extreme or undesirable then this may help find a way to combat LD and DD.
Scars are basically a type of fibrous tissue that takes the place of normal tissue after trauma, the tissue in question is not always the skin although this is the most obvious place of scarring both visually and in terms of frequency. In fact some animals are actually capable of regeneration of tissue rather than scar formation and indeed this is an area of research where I am sure a lot of work is being done.
The main components of both skin and scar tissue is collagen (those familiar with LD and DD will probably know about collagen as it is the main part of the lumps) but the difference between the 2 is in the way that it is put together as skin is normally random and scar tissue will repair in an organised fashion. Over expression of collagen in scars can lead to raised scars or keloids and of course over expression in other places can lead to DD and LD.
The normal cells that are in the skin are fibroblasts and for the purposes of scar formation they are transformed (that IS a scientific term and I don't mean transformed by magic) into myofibroblasts which are more capable of mass producing collagen. I have tried to avoid going into cell types in my recent reviews of scientific papers but the cells that are the main components of DD and LD nodules are myofibroblasts that have come from fibroblasts.
There are actually several treatments for scarring, that is to say that when it is going to be bad (to the extreme) there are things that are done to try to prevent it and some of these jumped out at me. The first one is radiation, much like in LD and DD this is used to limited effect to try and stop development of the scar but is only used in really bad cases as of course radiation means increased cancer risk. The other one that made my notes was steroid injections which again are used in the treatment of LD and DD. Also they noted that vitamin E was tried but didn't work (just like LD and DD).
So it is clear that scarring can be used in some ways as a model for LD and DD and if a treatment or something is found that helps to prevent scarring then maybe it can be used in LD and DD.
Signalling wise I can add another link in my diagram as TGF-B1 is known to be increased after damage so now we have.... (and I am finishing with this picture)