Key molecule explains why bones weaken with age
A first-of-its-kind study reveals that, as we age, levels of a certain molecule increase, which silences another molecule that creates healthy bone. It also suggests that correcting this imbalance may improve bone health, possibly offering new avenues for treating osteoporosis.
Osteoporosis affects around 200 million women worldwide.
One in 3 women and 1 in 5 men aged 50 and above are thought to experience a bone fracture in their lifetime as a result of osteoporosis.
In the United States, estimates indicate that 44 million people over 50 live with the condition, making it a major public health issue.
New research brings us closer to understanding the process that leads to bone degradation in osteoporosis and to potential new ways in which the condition could be tackled.
The findings explain a key molecular dynamic that accounts for the progressive frailty of our bones as we age.
Dr. Sadanand Fulzele, a bone biologist who works in the Department of Orthopaedic Surgery at Augusta University in Georgia, is a co-corresponding researcher and the last author of the new paper, which was published in the Journal of Gerontology: Biological Sciences.
Zooming in on a small molecular culprit
Dr. Fulzele and colleagues explain the process of bone formation — which starts with mesenchymal stem cells. These are stem cells that can be found in our bone marrow and that can go on to form as cartilage, bone, or the fat in bone marrow.
One of the factors that influence which form these cells will eventually take is a signaling molecule called stromal-cell-derived factor (SDF-1).
Previous research by the same team had shown how important SDF-1 is for the differentiation of mesenchymal stem cells into the different cells crucial to bone health.
Both in vitro and in vivo studies conducted by the researchers showed the key role of this signaling molecule for bone formation. SDF-1 is also important for bone repair and protects bone cells from oxidative stress, which is the imbalance between free radicals and antioxidants in the body that eventually leads to DNA damage and disease.
Also, previous studies had demonstrated that SDF-1 levels decline in aging mice; so, in this study, Dr. Fulzele and team wanted to understand precisely how this molecule's levels are regulated.
In some of his former research, Dr. Fulzele had shown that a small molecule called microRNA-141-3p stops vitamin C, a key antioxidant, from reaching our bone cells.
The team already knew that the molecule can stop mesenchymal stem cells from differentiating into other cells, as well as the fact that microRNA-141-3p increases with age. So, Dr. Fulzele and team hypothesized that microRNA-141-3p lowers SDF-1, and that this is one of the main ways in which this small molecule stops healthy bone formation.
