C/EBP homologous protein is necessary for normal osteoblastic function

C/EBP homologous protein (CHOP) suppresses adipogenesis and accelerates osteoblastogenesis in vitro. However, the effects of CHOP in the skeleton in vivo are not known. To investigate the actions of CHOP on bone remodeling, we examined the skeletal phenotype of chop null mice from 1 to 12 months of age. Chop null mice appeared normal and their growth and serum insulin like growth factor (IGF) I and osteocalcin levels were normal. X-ray analysis of the skeleton revealed no abnormalities and bone mineral density was normal. Static and dynamic histomorphometry revealed that chop null mice had decreased bone formation rates, without changes in osteoblast cell number, indicating an osteoblastic functional defect. The number of osteoblasts and osteoclasts and eroded surface were normal. Northern blot analysis revealed decreased type I collagen and osteocalcin mRNA levels in calvariae of chop null mice. In conclusion, chop null mice exhibit decreased bone formation and impaired osteoblastic function, indicating that CHOP is necessary for the normal expression of the osteoblastic phenotype.