Although experimentation with bone growth is still in very early stages, and has at this point only been tested on mice, this discovery has the potential to lead to treatments for a variety of conditions including osteoporosis and obesity.
“The production of bone could have a profound effect on the quality of life for the aging population,” says Hare, who is also the Louis Lemberg Professor of Medicine. “Around age 30 people begin to lose more bone mass than their bodies can create. One in three women and one in five men over the age of 50 will experience a hip fracture as a result of osteoporosis. By providing a way to produce more bone cells, MSCs create the potential to keep people active for much longer than previously possible and thus improve overall quality of life for seniors.”
The study, titled PPARγ Denitrosylation via S-nitrosoglutathione Reductase Participates in MSC-mediated Adipogenesis and Osteogenesis, was conducted using mice that lacked an enzyme that regulates the level of nitric oxide signaling. MSCs from these mice made more bone cells and fewer fat cells. Importantly this translated to leaner mice that had increased bone production. A specific factor in the MSCs was identified – PPARy – that determined whether the MSCs differentiated into either fat or bone-producing cells. This demonstrates that GSNOR-mediated PPARγ S-nitrosylation could be a pivotal checkpoint to regulate MSCs differentiation into adipocytes – cells specializing in fat storage – and osteoblasts – cells used in the formation of bone.
The results indicate more than an increase in bone density. The data shows that the GSNOR-mediated mice had a reduced body weight and a higher percentage of lean mass in comparison to the WT mice. This suggests that the procedure could be used to treat obesity in addition to bone frailty. The discovery highlights that mesenchymal stem cells do regulate important tissues in the body, and give researchers a path forward to design drugs that could modulate fat and bone development from the mesenchymal stem cells during adult life.
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