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Stanford study shows hedgehog proteins could enhance bone healing in diabetes

Diabetes impairs the activity of bone stem cells in mice, but activating these cells could help repair fractures, US scientists report.
Stanford University School of Medicine researchers found that applying a protein to a fracture site enhanced healing in the diabetic animals by increasing the expression of key signalling proteins.
“Here we’ve devised a feasible strategy for reversing a tissue-specific pathology – the inability to heal skeletal fractures efficiently – in a complex metabolic disease like diabetes,” said study author Dr Michael Longaker.
The researchers believe their findings explain why some people with diabetes struggle to heal efficiently from fractures. Longaker added this solution can be applied during surgery to help repair bone breaks.
Skeletal stem cells
Longaker and colleagues used mouse models of type 2 diabetes in their research and aimed to apply existing knowledge of skeletal stem cells (SSC) – shown previously to be a key part of fracture healing in mice – to the problem of impaired bone healing in diabetes.
Prior to the development of type 2 diabetes, the mice were able to heal leg bone fractures effectively. But diabetes led to the repaired bone becoming significantly weaker and the mice had lower SSC numbers than a control group of mice without diabetes.
A series of experiments led to the study team uncovering that the diabetic mice produced significantly less signalling proteins known as hedgehogs, which serve as a critical part of tissue regeneration and other biological processes.
When the control mice were exposed to a molecule that blocked the hedgehog signalling pathway, their bones were weaker and more brittle, like the diabetic mice.
Subsequent testing on the diabetic mice saw the molecule, applied in the form of a biologically friendly gel, improve healing when directed onto the fracture site.
Human samples
The research team then compared expressions of proteins important to the hedgehog signalling pathway with others obtained from human patients without diabetes.
“What we saw in these human samples completely echoed what we saw in the mice,” said study author Charles Cha, PhD. “The bones from the diabetic patients displayed significantly reduced expression of these important signalling proteins.
“We’ve looked to stem cells to learn why people with diabetes don’t heal bone fractures properly, and come up with an approach that we are excited to try in the clinic.”
Lead author Ruth Tevli, MD, and colleague will now conduct further research before testing this approach on human participants.
The study appears in the journal Science Translational Medicine.

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