Interestingly, the transgenic mice with Chop overexpressing showed impaired osteoblastic function and osteopenia owing to increased osteoblast apoptosis.46 Although further studies about the detailed mechanisms in the regulation of RANKL transcription are warranted, it is possible that the osteoclastogenic effect mediated by Chop found in this study also contributes to the osteopenia phenotype for Chop-overexpressing mice. This evidence concerns the gene TNFSF11 and Osteopenia.