the clock genes period 2 and cryptochrome 2 differentially balance bone formation生物钟基因周期2和色素2不同平衡骨形成.pdfVIP

The Clock Genes Period 2 and Cryptochrome 2 Differentially Balance Bone Formation 1 . 2.¤ 2 2 3 Erik Maronde * , Arndt F. Schilling , Sebastian Seitz , Thorsten Schinke , Isabelle Schmutz , 4 2 3 Gijsbertus van der Horst , Michael Amling , Urs Albrecht * 1 Dr. Senckenbergische Anatomie, Institute for Anatomy III, Goethe University, Frankfurt, Germany, 2 Department of Osteology and Biomechanics, University of Hamburg, Hamburg, Germany, 3 Unit of Biochemistry, Department of Medicine, University of Fribourg, Fribourg, Switzerland, 4 Department of Genetics, Centre for Biomedical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands Abstract Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry22/ 2 displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry22/ 2 displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type