Expression of CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) is induced during endoplasmic reticulum (ER) stress, which is related to apoptosis in several cell types. CHOP null mice have been exhibited to decrease bone formation. However, a study of transgenic mice overexpressing CHOP in the bone microenvironment showed that CHOP overexpression impairs the osteoblastic function leading to osteopenia. The regulatory role of CHOP in bone formation is controversial and still remains to be clarified. Here, we investigated the alterations in bone microstructure of CHOP knockout (Chop −/− ) mice and tested the gender difference of CHOP deficiency in susceptibility to osteopenia. Adult female and male mice (WT) and Chop −/− mice were used. The microcomputed tomography (µCT) analysis in trabecular bone and cortical bone of tibia was determined. Trabecular bone volume fraction (BV/TV), trabecular number, and bone mineral density (BMD) in tibia are markedly decreased in both male and female Chop −/− mice compared to the control WT mice. Unexpectedly, the BMD and BV/TV in trabecular bone of tibia in female Chop −/− mice were significantly lower than in male Chop −/− mice. The similar results could also be observed in the cortical bone of tibia in Chop −/− mice. This gender difference was also observed in the decreased capacity of osteoblast differentiation of bone marrow cells isolated from Chop −/− mice. These results indicated that ER stress-related CHOP signaling might play an important role in the bone formation in a mouse model, especially in females. There is the gender difference of CHOP deficiency in susceptibility to osteopenia.
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