Interferon gamma important for skeletal integrity in mice
MedWire News: Interferon gamma (IFNγ) plays a key role in the maintenance of skeletal integrity, report researchers who suggest that the cytokine may potentially be used therapeutically to improve bone strength.
Gustavo Duque (The University of Sydney, Australia) and colleagues showed that disruption of IFNγ signaling in mice results in an osteoporotic phenotype with low bone turnover, and that administration of IFNγ increases bone mass and strength in a mouse model of osteoporosis.
The researchers previously reported that IFNγ is required for the osteogenic differentiation of mesenchymal stem cells in vitro and for the maintenance of bone mineral density (BMD) in vivo.
Based on these findings, they explored the role of IFNγ in bone turnover in genetically modified mice that do not express the IFNγ receptor (IFNγR1-/-). Duque and team report in the Journal of Bone and Mineral Research that bone volume was 45% lower in IFNγR1-/- mice compared with their wild-type littermates (IFNγR1+/+).
Other bone structural parameters, including trabecular thickness and number and cortical thickness were also significantly reduced in IFNγR1-/- mice compared with wild-type animals.
Consistent with these findings, bone histomorphometry showed a significant reduction in mineralized surfaces, bone formation rate, and mineral apposition rate in IFNγR1-/- mice relative to wild-type mice. Significant reductions in osteoblast and osteoclast numbers, and in circulating levels of bone formation and bone resorption markers were also observed among the IFNγR1-/- mice.
To examine whether treatment with IFNγ could improve BMD and bone microarchitecture in a model of osteoporosis, the researchers administered IFNγ (2000 and 10,000 units) to wild-type ovariectomized and sham-operated mice.
Among sham-operated mice, those treated with IFNγ 10,000 units had significantly higher BMD than vehicle-treated animals (0.070 vs 0.058 g/cm2). In addition, a 17% reduction in BMD induced by ovariectomy was canceled out by IFNγ treatment at both of the experimental doses.
"Our findings directly demonstrate that disruption of IFNγ signaling affects bone remodeling through a reduction in bone formation," Duque and co-authors remark.
They conclude: "Further studies are required to examine the therapeutic potential of targeting this novel signaling pathway in human osteoporosis."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Laura Dean