We acknowledge Jean-Sebastien Binette (Centre for Bone and Periodontal Research) and Jacinthe Sirois (Québec Transgenic Research Network) for excellent technical assistance. We are grateful to Erique Lukong, Daniel Larocque, and Mark Bedford for helpful discussions. This work was supported by grant MT13377 to SR and grant MOP-13419 to JEH from the Canadian Institutes of Health Research (CIHR). SR holds an Investigator Award from the CIHR and JEH is a Chercheur Boursier, Senior of the FRSQ. Competing interests. The authors have declared that no competing interests exist. Author contributions. SR and JEH conceived and designed the experiments. SR, NT, GVF, GAT, TC, GV, MM, PC, AFR, SK, WL, AL, and YJG performed the experiments. SR and JEH analyzed the data. MLT generated the mice. SR and JEH wrote the paper. A previous version of this article appeared as an Early Online Release on November 11, 2005 (DOI: 10.1371/journal.pgen.0010074.eor). Abbreviations ALP alkaline phosphatase BMC bone mineral content BMD bone mineral density BMP-2 bone morphogenetic protein-2 CT computed tomography CTX C-telopeptide MEF mouse embryo fibroblast PPARγ peroxisome proliferator–activated receptor γ shRNA short hairpin RNA TRAP tartrate-resistant acid phosphatase