It may be possible to accelerate bone healing to help patients recover from fractures and breaks in a much shorter time frame. This would be particularly beneficial in patients with osteoporosis or diabetes, where bone healing is much slower. New research could have identified a mechanism that could be harnessed to do just that.
It has previously been shown that bone stem cells are involved in the maintenance and repair of bone, but the mechanisms involved are not well understood. Bone stem cells have been found in the outer layer of bone – the periosteum – and also in the bone marrow. While both are similar, they appear to be controlled by different regulatory mechanisms, and the properties of the stem cells are different. each population of bone stem cells has functions that the other does not.
The researchers focused their attention on periosteum stem cells, which are the least understood of the two stem cell populations. Periosteum stem cells are known to play a role in shaping of bone, bone thickness, and fracture repair. There are also subpopulations of stem cells, but little was known about the roles each subpopulation plays and how those subpopulations are regulated.
The researchers developed a method of identifying those subpopulations and attached markers to each in mouse models. They were able to determine how they contributed to bone repair and some of the factors that regulate migration and proliferation.
The researchers found that periosteum stem cells play a greater role in bone fracture repair than bone marrow stem cells and that they are triggered by a mechanical injury to bone. The stem cells respond to chemokines, which are inflammatory molecules produced following an injury to bone, especially to chemokine CCL5.
Chemokine CCL5 binds to receptors on the surface of the stem cells and triggers migration of the stem cells to the injured area of the bone. In mice deficient in chemokine CCL5, bone healing was delayed and was accelerated when chemokine CCL5 was introduced into chemokine CCL5-deficient mice.
“We think this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties regulated by specific mechanisms,” said Dr. Dongsu Park, corresponding author of the study. “We have identified markers that enable us to tell bone stem cell subtypes apart and studied what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries.”
The study is detailed in the paper – Identification of Functionally Distinct Mx1 αSMA Periosteal Skeletal Stem Cells – which was recently published in the journal Cell Stem Cell. DOI: 10.1016/j.stem.2019.11.003