While interferon gamma sounds like an outer space weapon, it's actually a hormone produced by our own bodies, and it holds great promise to repair bones affected by osteoporosis. In a new study published in the journal Stem Cells, researchers from the Research Institute of the McGill University Health Centre explain that tweaking a certain group of multipotent stem cells (called mesenchymal stem cells) with interferon (IFN) gamma may promote bone growth.
"We have identified a new pathway, centered on IFN gamma, that controls the bone remodelling process both in-vivo and in-vitro," explains Dr. Kremer, the study's lead author and co-director of the Musculoskeletal Axis of the McGill University Health Centre. "More studies are required to describe it more precisely, but we are hopeful that it could lead to a better understanding of the underlying causes of osteoporosis, as well as to innovative treatments."
From cell culture to animal model
"First, we stimulated cultured mesenchymal stem cells to turn into bone cells (osteoblasts) in-vitro," says Dr Richard Kremer, a Professor with the McGill's Faculty of medicine. "We realised that this differentiation process involved IFN gamma-related genes, but also that these bone cells precursors could both be stimulated by IFN gamma and produced IFN gamma."
The next step was to move to an animal model where IFN gamma effect is blocked by inactivating its receptor, a model called IFN gamma receptor knock-out. Bone density tests, comparable to those used to diagnose people with osteoporosis, were conducted. The results revealed that these animals have significantly lower bone mass than their healthy counterparts In addition, their mesenchymal stem cells have a decreased ability to make bone. "These findings confirm that IFN gamma is an integral factor for mesenchymal stem cells' differentiation into osteoblasts also in-vivo," says Dr. Kremer.
New biological pathway, now hope for treatments
Both in-vitro and in-vivo results proved that IFN gamma is key to the differentiation of mesenchymal cells into bone cells, and to growth process of the bone. The exact pathway by which IFN acts on bone cells' formation will require more research to be described, but the strict correlation highlighted in this study leaves no doubt on its importance.
Until now, IFN gamma has been mostly used as an agent to prevent infections and to reinforce the immune system from illnesses such as cancer. These findings provide hope that IFN gamma itself, or another molecule involved in its pathway, could soon also become an efficient drug-target for an antidote for osteoporosis.
Osteoporosis is a disease in which bones become fragile and more likely to break. If left untreated, osteoporosis can progress painlessly until a bone fractures in the hip, spine and wrist. According to the World Health Organization, osteoporosis affects one in four women over the age of 50.
This study was supported by the Canadian Institutes for Health Research, the Dairy Farmers of Canada, the Natural Sciences and Engineering Research Council of Canada and the Fond de la Recherche en Santι du Quιbec.
- Richard Kremer, Gustavo Duque, Dao Chao Huang, Michael Macoritto, Xian Fang Yang, and Daniel Rivas. Autocrine Regulation of Interferon gamma in Mesenchymal Stem Cells Plays a Role in Early Osteoblastogenesis. Stem Cells, (in press)
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