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.
Knee Bones
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 fractures.
Osteoporosis develops particularly in older people. Today, a new study could eventually lead to the development of therapeutic strategies to improve bone regeneration in these patients. Results published in the journal Cell Stem Cell on the 5th December 2019 have laid out 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 bone. Previous studies have shown that these two populations of stem cells share many characteristics; however, they 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.
Of these two populations, periosteal stem cells are the least known. Although 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.
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CCL5 chemokine
Here, however, Dr. 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.
The researchers 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 Dr. Dongsu Park.
In conclusion, this study has allowed for the identification of different stem cell subtypes and their distinguishing markers, and their roles in bone repair. This discovery gives insight into new therapeutic strategies for the treatment of bone damage in adults, particularly in the setting of osteoporosis or diabetes. Indeed, people with diabetes may be prone to falls and fractures due to 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.
References
Ortinau, L. C., Wang, H., Lei, K., Deveza, L., Jeong, Y., Hara, Y., Grafe, I., Rosenfeld, S. B., Lee, D., Lee, B., Scadden, D. T., & Park, D. (2019). Identification of functionally distinct Mx1⁺αSMA⁺ periosteal skeletal stem cells. Cell Stem Cell, 25(6), 784–796.e5. https://doi.org/10.1016/j.stem.2019.11.003