Osteoporosis is a disease of the bones that happens when you lose too much bone, make too little bone or both. Scientists at The Scripps Research Institute (TSRI) have identified a new therapeutic approach that, while still preliminary, could promote the development of new bone-forming cells in patients suffering from bone loss.
The TSRI study focused 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. Since these mesenchymal stem cells can develop into several different types of cells - including fat, connective tissues, bone and cartilage, they have a number of potentially important therapeutic applications.
AdvertisementThe researchers 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, they combined a variety of structural biology approaches to rationally design a new compound that could repress the biological activity of PPARy. The results showed that when human mesenchymal stem cells were treated with the newly developed compound, which they called SR2595 (SR-Scripps Research), there was a statistically significant increase in osteoblast formation, a cell type known to form bone.
Researcher Patrick Griffin said, "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. 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."
The study is published in the Nature Communications.
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