The inflammation in type 2 diabetes alters the ‘Hedgehog’ signaling, which makes skeletal stem cells impossible to be correctly activated.
Diabetes is a disease in which, either because of the inability of the organism to produce insulin - type 1 diabetes - or to use it correctly - type 2 diabetes -, the bloodstream transports an abnormally high amount of glucose that ends up damaging numerous organs.
Consequently, diabetes patients have a higher risk of multiple disease development, as well as bone fractures.
More;Diabetes causes, once a fracture occurs in a bone, this is more difficult to heal.And now, researchers at the Stanford University Faculty (USA) have discovered not only why the population with diabetes has a lower capacity to heal their fractures, but also the way to correct this situation.
As Michael Longaker, director of this research published in the magazine "Science Translational Medicine" explains, "we have discovered the reason why some diabetic patients do not recover well from their bone fractures.And also, we have found a solution that can be locally applied during surgery to repair this damage.
Diabetes is increasingly frequent worldwide, and any improvement in the ability of those affected to recover from their fractures could have a greatly positive effect on their quality of life ».
quantity and quality
The authors had already observed in a previous study with animal models - the presence in the bones of a type of stem cells - bounded as 'skeletal stem cells' - with the ability to differentiate in any component of the skeleton, whether they were the bones,cartilage or bone marrow stroma.In fact, the elimination of these skeletal stem cells reduced the ability to ‘healing’ of the bone fractures of animals.
Therefore, as indicated by Charles Chan, co-author of the investigation, “we wanted to apply what we already knew about skeletal stem cells to the problem of diminished bone reparation capacity of people with diabetes.Does the disease affect the healing of fractures in some way modulating the activity of these stem cells?
We have discovered the reason why some diabetic patients do not recover well from their bony longaker bone fractures
To answer this question, the authors used mice with type 2 diabetes, animals in which the disease develops when reaching the fourth week of life.And what they saw is that the younger animals - that is, ‘prediabetic’ - had a totally normal healing capacity.On the contrary, and once the diabetes had been presented, the ‘repaired’ bones were much weaker and much less dense than those of animals without the disease.And this, what could be due?As the researchers analyzed the amount of skeletal stem cells in the healing bones, finding that the diabetic mice had a significantly lower figure of this type of cells than the ‘control’ animals.
So, is it a quantity problem?Well, in part yes, but also of functionality.And it is that skeletal stem cells in diabetes, in addition to less numerous, have a lower regenerative capacity.And not because they are not completely functional, which they are.It is that they are not correctly activated by cell signals, since animals with the disease produce much lower levels of signaling proteins - consciously, of the so -called signaling route 'Hedgehog' - that play a critical role in embryonic development andin thetissue regeneration.In fact, the blockade of this signaling route caused the control mice to have, which their diabetic homonyms, a decreased capacity to repair their bone fractures.
Thus, as Michael Longaker points out, “the next step was to evaluate whether the addition of proteins from the‘ Hedgehog ’signaling in the areas of fractures in diabetic animals restored their ability to cure these lesions.And what we saw is that the animals were cured as their homonyms without diabetes ».
Finally, the authors took bone samples of humans with diabetes that had undergone replacement surgery of a joint damaged by osteoarthritis.And what they observed is that, as was the case in animal models, the expression of protein of the ‘Hedgehog’ signaling was very diminished.
Possible treatment
Researchers believe that the inhibition of the ‘Hedgehog’ signaling in diabetes is caused by inflammation associated with the disease.Or more specifically, by the elevation of the levels of the tumor necrosis alpha (TNF-α) factor caused by this inflammation.Not surprisingly, mice with diabetes used in their experiments showed abnormally high levels of TNF-α.And to this it is added that the results showed that the high levels of TNF-α inhibited the expression of some proteins of this signaling.
Therefore, can it be deduced that the inhibition of TNF-α activity could restore the repair capacity of bone fractures in the population with diabetes?Well, at least in theory, yes.The problem is that this factor performs very important biological functions, so its inhibition could have very harmful consequences for patients.
Be that as it may, Michael Longaker concludes, «in our work we show a feasible strategy to reverse a specific tissue pathology, that is, the inability to an efficient repair of bone fractures, in a complex metabolic disease such as diabetes.All this by applying a compound to stimulate the activity of adult stem cells.Thus, we can anticipate that mediated molecular therapies by the ‘Hedgehog’ signaling and that they act directly on stem cells could constitute effective human treatment ».
