Scientists find way to boost bone-forming cells, raising osteoporosis prospects

While the findings are early, scientists are hopeful that bone loss disease could find a new treatment after their lab work succeeds in increasing the formation of bone.

Osteoporosis is not the only potential target – scientists say aging, obesity and diabetes could be, too.

The researchers are from the Florida campus of The Scripps Research Institute, and they publish their work in the journal Nature Communications.

The study investigated a protein known as PPARG and examined its effect on bone marrow stem cells (mesenchymal stem cells).

Already knowing that a partial loss of PPARG in a genetically modified mouse model led to an increase in osteogenesis, they did more work using the approaches of structural biology.

The scientists wanted to mimic the effect on PPARG to increase bone formation by use of a drug candidate – they rationally designed a new compound that would repress the protein.

In the experiment, when human mesenchymal stem cells were treated with the new compound, labeled SR2595, there was a statistically significant increase in osteoblasts, the cells responsible for forming bone.

Patrick Griffin, PhD, chair of the department of molecular therapeutics and director of the Translational Research Institute at Scripps Florida, says this protein had already been targeted pharmaceutically:

“These findings demonstrate for the first time a new therapeutic application for drugs targeting PPARG, which has been the focus of efforts to develop insulin sensitizers to treat type 2 diabetes.”

SR2595 holds potential for a number of therapies

Since the mesenchymal stem cells that were treated can develop into several different cell types, including fat, connective tissues, bone and cartilage, there is potential for a number of therapies, as Prof. Griffin says:

Osteoporosis

• Osteoporosis is a bone disease affecting structure and strength
• Risk factors include avoidable ones such as smoking
• No symptoms are caused by the loss of bone density itself.

Learn more about osteoporosis

“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.”

First author of the study David Marciano adds:

“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.”

Dr. Marciano will investigate the following for the department of genetics at Stanford University, CA:

“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.”

US guidelines for the prevention of osteoporosis mean that up to three quarters of white women aged over 65 years have become candidates for drug treatment – but most hip fractures occur in those without the disease. Hip fracture drug prevention strategies are “pointless,” therefore, said a leading orthopedic specialist in May.

Written by Markus MacGill