The Scripps Research Institute (TSRI), Florida, have made a breakthrough in bone treatment: a method manipulate a protein that could lead to the development of new bone-forming cells. The finding which was published in the journal Nature Communications is a harbinger of great news for patients suffering from increasing bone loss.
The study laid emphasis on a protein called PPARy (known as the master regulator of fat) and its impact on the fate of stem cells derived from bone marrow (mesenchymal stem cells). Since these mesenchymal stem cells can develop into several different cell types — including fat, connective tissues, bone and cartilage — they have a number of possibly crucuial treatment applications. The scientists knew that a partial loss of PPARy in a genetically modified mouse model led to increased bone formation.
To see if they could mimic that effect using a drug candidate, the researchers designed a new compound that could repress the biological activity of PPARy. The results showed that when human mesenchymal stem cells were treated with the new compound, which they called SR2595, there was a statistically significant increase in osteoblast formation, a cell type known to form bone.
“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 sensitisers to treat type 2 diabetes,” said 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, ageing, obesity and diabetes,” Griffin added.
Apart from recognizing a potential new treatment for bone loss, the study may even broaden our horizons regarding other bone treatment options.
“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,” said David P. Marciano, first author of the study.