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Regulator of Osteoclast Formation Identified in Mice
NEW YORK (Reuters Health) Dec 03 - New research suggests that a key inhibitor of osteoblast differentiation is also the molecule that regulates osteoclast formation, a finding that could have important implications for anti-diabetes agents that target this molecule.
Peroxisome proliferator-activated receptor (PPAR)-gamma has been shown to activate adipogenesis and repress osteoblast generation. Whether PPAR-gamma had any effect on osteoclasts, however, was unclear, according to the report in the December 2nd online issue of Nature Medicine.
Using a murine model, Dr. Ronald M. Evans and colleagues from the Salk Institute for Biological Studies in La Jolla, California, show that osteoclast differentiation is impaired when PPAR-gamma is absent.
Animals lacking PPAR-gamma had skeletons with increased bone mass. In addition, the medullary cavity space was decreased and extramedullary hematopoiesis was seen in the spleen.
By contrast, when PPAR-gamma activity was stimulated with rosiglitazone, a commonly used anti-diabetes agent, the animals displayed decreased bone density.
Further analysis suggested that PPAR-gamma achieves its effects by directly regulating c-fos expression, an established mediator of osteoclast formation.
\"These findings have potential clinical implications, as they suggest that long-term rosiglitazone usage in the treatment of type 2 diabetes and insulin resistance may cause osteoporosis, owing to a combination of decreased bone formation and increased bone resorption,\" the authors conclude.
Nat Med 2007 |
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发表于 2007-12-20 10:23:45