Gender difference of CCAAT/enhancer binding protein homologous protein deficiency in susceptibility to osteopenia

Cheng-Tien Wu; Ya-Wen Chen; Yen-Hao Su; Chen-Yuan Chiu; Siao-Syun Guan; Rong-Seg Yang; Shing-Hwa Liu

doi:10.1002/jor.24264

Gender difference of CCAAT/enhancer binding protein homologous protein deficiency in susceptibility to osteopenia

J Orthop Res. 2019 Apr;37(4):942-947. doi: 10.1002/jor.24264. Epub 2019 Mar 28.

Authors

Cheng-Tien Wu¹, Ya-Wen Chen², Yen-Hao Su^{1

3}, Chen-Yuan Chiu⁴, Siao-Syun Guan⁵, Rong-Seg Yang⁶, Shing-Hwa Liu^{7

8

9}

Affiliations

¹ Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
² Department of Physiology and Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
³ Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Institute of Food Safety and Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁵ Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.
⁶ Department of Orthopaedics, College of Medicine, National Taiwan University, No.1, Jen-Ai Road, Section 1, Taipei 10051, Taiwan.
⁷ Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
⁸ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
⁹ Institute of Toxicology, College of Medicine, National Taiwan University, No.1, Jen-Ai Road, Section 1, Taipei 10051, Taiwan.

PMID: 30835896
DOI: 10.1002/jor.24264

Abstract

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. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Keywords: C/EBP homologous protein; gender difference; osteoblastogenesis; osteopenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Density
Bone Diseases, Metabolic / diagnostic imaging
Bone Diseases, Metabolic / etiology*
Female
Male
Mice, Knockout
Sex Characteristics*
Transcription Factor CHOP / physiology*
X-Ray Microtomography

Substances

Ddit3 protein, mouse
Transcription Factor CHOP