According to a study published in Journal of Gerontology: Biological Sciences, a small molecule was discovered to play a role in bone formation, ultimately inspiring drug discovery. The molecule is a microRNA-141-3p signaling molecule that is the stromal-cell-derived factor, or SDF-1. "If you are 20 years old and making great bone, you would still have microRNA-141-3p in your mesenchymal stem cells. But when you are 81 and making weaker bone, you have a lot more of it," explains Dr. Sadanand Fulzele, a researcher at the Medical College of Georgia at Augusta University.
According to the International Osteoporosis Foundation, about 30 percent of postmenopausal women in the United States and Europe have been diagnosed with osteoporosis with at least 40 percent of these women sustaining one or more fractures in their lifetime. Additionally, 15-30 percent of men diagnosed with osteoporosis will also suffer one or more fractures.
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SDF-1 is significant in osteoporosis and overall bone health. It regulates the differentiation of mesenchymal stem cells into the major components of our skeletal system. SDF-1 also holds other roles such as guiding mesenchymal stem cells during bone formation and repair and protecting cells from oxidative stress.
The role of SDF-1 in aging bone grabbed the attention of researchers to understand its regulation and they hypothesized that a decrease in SDF-1 affects microRNA-141-3p on the healthy differentiation of mesenchymal stem cells. The scientists also had already found it could hinder that important differentiation of mesenchymal stem cells and knew levels of microRNA-141-3p increase with aging. Their animal studies had indicated that oxidative stress in mesenchymal stem cells decreases SDF-1 and that the signaling molecule could protect those cells from death by oxidative stress. Additionally, in continuation of their hypothesis, the researchers added microRNA-141-3p to cells and observed worsening bone function, they then added an inhibitor and saw improvement.
Ultimately, the research findings can inspire clinical-grade drugs that can be used to inhibit microRNA-141-3p in bone diseases, like osteoporosis. "It normalizes bone function. We think clinical-grade inhibitor may help us do the same in people,” says William D. Hill, stem cell researcher and faculty member at the Medical University of South Carolina. "We have identified a number of microRNAs that change in the bone marrow stem cells with aging and we are going after each one of these to understand how they are working and are they working together or independently," he adds. "We are starting to take more of a biological systems approach, not just changing one target molecule, but looking at how this network of molecules is changed with age or disease and how we can reach in and sort of reset these different pathways."