Researchers at Baylor College of Medicine have discovered a new mechanism that helps maintain and repair bones in adults. Ultimately, this could help develop new therapeutic strategies to improve bone healing.
Osteoporosis is a skeletal disease characterized by reduced bone density and changes in the microarchitecture of bones. These changes weaken the bone and increase the risk of fracture. This disease develops particularly in older people. Today, a new study could eventually lead to the development of therapeutic strategies to improve bone healing in these patients. According to the results published in the journal Cell Stem Cell on the 5th December, 2019 researchers have discovered a new mechanism that contributes to the maintenance and repair of bones in adults.
“Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum — the outer layer of tissue — that envelopes the bone. Previous studies have shown that these two populations of stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms. “said Dr. Dongsu Park, assistant professor of molecular and human genetics, pathology and immunology at Baylor College of Medicine, where the study was conducted.
Of these two populations, periosteal stem cells are the least known. Although the scientists know that this is a heterogeneous population of cells that can contribute to the thickness, formation and repair of bone fractures, no one has yet been able to distinguish between the different subtypes of bone stem cells in order to study the regulation of their different functions.
Here, however, Dongsu Park and colleagues were able to develop a technique in mice to identify different subpopulations of periosteal stem cells, define their contribution to the repair of bone fractures and identify the specific factors that regulate their migration and proliferation under physiological conditions.
In rats, they discovered specific markers for this class of cells. They identified a specific subset of stem cells that contribute to lifelong bone regeneration in adults. They also observed that periosteal stem cells react to inflammatory molecules, chemokines, which are normally produced in bone injuries.
In detail, periosteal stem cells have receptors that bind to the CCL5 chemokine. The CCL5 chemokine sends a signal to the cells to migrate to the injured bone and repair it. By suppressing the CCL5 gene in rats, the researchers found defects in bone repair that delayed healing. However, when they gave CCL5 to rats that had lost CCL5, the bones recovered faster.
New therapeutic strategies for treating bone damage in adults
“Our findings contribute to a better understanding of the healing of adult bones. We believe this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties that are regulated by specific mechanisms,” said Dongsu Park. We have identified markers that allow us to distinguish between the subtypes of bone stem cells and have investigated what each subtype contributes to bone health. The understanding of how the functions of bone stem cells are regulated offers the possibility of developing new therapeutic strategies for the treatment of bone damage in adults.
In the long term, these findings may therefore have potential therapeutic applications, particularly in people with osteoporosis or diabetes. Indeed, people with diabetes may be prone to falls and fractures due to possible neurological, visual or renal complications. In addition, bone fragility in diabetics is likely to be due to changes in bone remodeling and, in particular, an increase in bone resorption.