Researchers identify a potential new treatment for osteoporosis
Scientists from The Scripps Research Institute (FL, USA) have identified a new therapeutic approach that, while still preliminary, could promote the development of new bone-forming cells in patients suffering from osteoporosis.
The study specifically focused on a protein called PPARy (known as the master regulator of fat) and its impact on the fate of mesenchymal stem cells. Since mesenchymal stem cells are able to develop into several different cell types—including fat, connective tissues, bone and cartilage—they are known to have a number of potentially important therapeutic applications. The findings were recently published in Nature Communications.
The research team knew that a partial loss of PPARy in a genetically modified mouse model led to increased bone formation. To see if they could mimic this effect using a drug candidate, the researchers combined a variety of structural biology approaches to rationally design a new compound that could repress the activity of PPARy.
The results demonstrated that when human mesenchymal stem cells were treated with the new compound, called SR2595 (SR=Scripps Research), there was a statistically significant increase in osteoblast formation, an essential cell type in bone development.
“These findings demonstrate for the first time a new therapeutic application for drugs targeting PPARy, which has been the focus of efforts to develop insulin sensitizers to treat type 2 diabetes,” explained Patrick Griffin director of the Translational Research Institute at Scripps Florida. “We have already demonstrated SR2595 has suitable properties for testing in mice; the next step is to perform an in-depth analysis of the drug’s efficacy in animal models of bone loss, aging, obesity and diabetes.”
In addition to identifying a potential new therapeutic for bone loss, the study may have even broader implications. “Because PPARG is so closely related to several proteins with known roles in disease, we can potentially apply these structural insights to design new compounds for a variety of therapeutic applications,” commented David P. Marciano, first author of the study. “In addition, we now better understand how natural molecules in our bodies regulate metabolic and bone homeostasis, and how unwanted changes can underlie the pathogenesis of a disease.”
David P. Marciano, Dana S. Kuruvilla, Siddaraju V. Boregowda et al. Pharmacological repression of PPARγ promotes osteogenesis. Nature Communications, doi: 10.1038/ncomms8443 (2015) [Epub ahead of print]; The Scripps Research Institute press release: https://www.scripps.edu/news/press/2015/20150612griffin.html