Researchers have identified a potential new treatment for osteoporosis that could promote the development of new bone-forming cells.
The potential new method focuses on a protein called PPARy and how it impacts bone marrow-derived stem cells, Scripps Research Institute reported. These cells can develop into fat, connective tissue, cartilage and bone.
A partial loss of PPARy in genetically modified mice has been shown to increase bone formation, and researchers set out to create a drug that mimicked this effect. They combined a variety of structural biology approaches to create a new compound that restricts the biological activity of PPARy.
The findings showed that when human mesenchymal stem cells were treated with the new compound, dubbed SR2595, there was a significant increase in bone cell formation.
"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," said Patrick Griffin, chair of the Department of Molecular Therapeutics and 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."
The study offers a promising new therapy for bone loss, but the researchers suggest it could have additional applications.
"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, a recent graduate of TSRI's PhD program and former member of the Griffin lab. "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."
The findings were published in a recent edition of the journal Nature Communications.
