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SCIENCE AT WORK Mending Brittle Bones BY EMMA WALTON Astrophysics The Early Universe in Focus The European Space Agency’s (ESA) Planck satellite has stopped collecting data since August 2013, yet full analysis of these observations will keep astrophysicists busy for at least a decade. Two years ago, researchers from the Planck collaboration thus published the most precise map ever of the temperature fluctuations in the cosmic microwave background radiation (CMB)—the oldest light in the Universe, emitted some 380,000 years after the Big Bang. They are now studying the polarization of this fossil radiation, caused by the interaction of light with the matter it went through. The researchers are thus able to retrace the tumultuous history of our Universe from its infancy to the present day. 14 CNRS INTERNATIONAL MAGAZINE A patch of the southern sky based on observations performed by ESA’s Planck satellite at microwave and sub-millimeter wavelengths. Micro-X-ray tomography of mouse metatarsals treated with Dock5 inhibitor C21 (left), and untreated (right). © ESA/PLANCK COLLABORATION With population ageing, the prevalence of osteoporosis, a progressive bone disease, is on the rise. Yet current treatments are far from satisfactory. Now, CRBM1 researchers led by Anne Blangy have come up with a novel therapeutic strategy that shows great promise in animal models.2 Our skeleton is remodeled throughout life. Cells called osteoclasts remove or “resorb” old bone, while osteoblasts deposit newly- formed bone. These processes are normally balanced but in osteoporosis, the scales tip in favor of osteoclasts, leading to loss of bone density and susceptibility to fractures. Postmenopausal women are most at risk because low estrogen levels increase osteoclast activity. Most treatments for osteoporosis eliminate osteoclasts. Yet these cells also secrete proteins that stimulate osteoblast growth, so wiping them out completely impairs bone formation. Blangy’s team put forward a new strategy to tackle these rogue cells. During resorption, osteoclasts form a tight seal on bone, “much like a plunger over a blocked drain,” explains Blangy. They then secrete acid and proteases, which break down bone. “If we can prevent the formation of this seal, then we may block bone resorption while preserving the other functions of osteoclasts,” she adds. After years of research, Blangy’s team identified an essential component of the osteoclast seal called Dock5. Finally, the researchers could test their theory in an animal model. Like humans, mice with low estrogen levels are prone to osteoporosis and those that have had their ovaries removed develop the condition within weeks. Blangy treated these mice with an inhibitor of Dock5 called C21 before measuring bone density and markers of bone turnover. Remarkably, treatment with C21 provided effective protection against bone loss without limiting the formation of new bone. Blangy hopes that investment from the pharmaceutical industry will help make C21 or C21-based molecules readily available in health institutions and allow patients with osteoporosis to put a spring back in their step. ii Biology 1. Centre de recherche de biochimie macromoléculaire (CNRS / Université de Montpellier). 2. V. Vives et al., “Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation,” Nature Communications, 2015. 3(6): 6218. © G. CRES/CNRS/CRBM anne.blangy@crbm.cnrs.fr


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