title: The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation.
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.
  
  
  RESULTS
  We found that Per2(Brdm1) mutant mice as well as mice lacking Cry2(-/-) displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2(Brdm1) mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2(-/-) displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2(-/-) mutants despite the simultaneous inactivation of Per2.
  
  
  CONCLUSIONS
  This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters.
authors.affiliation: Dr. Senckenbergische Anatomie, Institute for Anatomy III, Goethe University, Frankfurt, Germany. E.Maronde@em.uni-frankfurt.de
authors.forename: Erik
authors.initials: E
authors.lastname: Maronde
authors.forename: Arndt F
authors.initials: AF
authors.lastname: Schilling
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seitz
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schmutz
authors.forename: Gijsbertus
authors.initials: G
authors.lastname: van der Horst
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Urs
authors.initials: U
authors.lastname: Albrecht
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D056931:Cryptochromes / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D056950:Period Circadian Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C538967:Cry2 protein, mouse; D056931:Cryptochromes; D056950:Period Circadian Proteins