title: Signal transducer and activator of transcription 3 regulates CCAAT-enhancer-binding homologous protein expression in osteoblasts through upregulation of microRNA-205.
abstract: The transcription factor, CCAAT-enhancer-binding protein homologous protein (CHOP), is induced by endoplasmic reticulum-stress and mediates programmed cell death. In osteoblasts, CHOP overexpression increases the rate of apoptosis, leading to osteoblastic dysfunction. However, the regulatory mechanisms underlying CHOP expression remain unclear. In the present study, western blot analysis was used to demonstrate that the activation of signal transducer and activator of transcription 3 (STAT3) inhibited the levels of the CHOP protein, whereas small interfering RNA-mediated the knockdown of STAT3 upregulated CHOP expression. Furthermore, STAT3 was shown to increase the expression level of microRNA (miR)-205. A luciferase reporter assay revealed that miR-205 was able to directly target the 3'-untranslated region of the CHOP gene to inhibit its protein expression. The miR-205 antisense largely abolished the inhibitory effect of STAT3 activation on the levels of CHOP protein. Therefore, the results demonstrated a previously unknown STAT3/miR-205/CHOP signaling pathway in osteoblasts, which may aid the understanding of the pathogenic mechanisms of associated diseases, including osteoporosis.
authors.affiliation: Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China.
authors.forename: Fugen
authors.initials: F
authors.lastname: Pan
keywords: CCAAT-enhancer-binding homologous protein; microRNA-205; osteoporosis; signal transducer and transcription activator 3