PAF-way to bone loss

Many women after menopause suffer from the bone disease osteoporosis, where there is an increase in bone re-absorption back into the body; this creates a high risk for bone fracture. A great deal of research has gone into dissecting the molecular underpinnings of this debilitating and painful disease. One gene that has been implicated in bone resorption diseases is platelet-activating factor or PAF.

Now, Satoshi Ishii and colleagues, at the University of Tokyo, provide a potential new arena for treating such bone diseases through their characterization of bone loss in mice where the receptor for PAF has been removed, thus effectively inhibiting PAF function. To simulate menopause, these mice had their ovaries removed. The researchers found that in mice without the PAF receptor, ovarectomized mice had greatly improved bone mineral density as well as bone volume compared to ovarectomized mice that still had PAF gene function.

Further molecular studies in these mice showed that osteoclasts (the bone cells that responsible for the breakdown of bone material) are responsible for PAF's mechanism of action. In addition, when mice were treated with a molecule that inhibits PAF receptor function, bone resorption was also reduced. These data indicate that inhibition of PAF activity presents a possible strategy for treating osteoporosis and other bone resoprtion diseases.

View the PDF of this article at: http://www.jci.org/cgi/content/full/114/1/85

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