机构：[1]Department of Immuno-oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China临床科室肿瘤免疫科河北医科大学第四医院[2]Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642,USA[3]Institute of Chinese Minority Traditional Medicine, MINZU University of China, Beijing 100081, China[4]Centerfor Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture. However, the effects of CLP on bone metabolism are unknown. Here, we demonstrate that WT mice treated with CLP for 2 weeks had significantly reduced trabecular bone volume and cortical bone thickness, associated with increased osteoclast (OC) numbers, but had no change in osteoblast numbers or bone formation rate. Bone marrow cells from CLP-treated mice had normal OC precursor frequency, but formed significantly more OCs when they were cultured with RANKL and M-CSF. CLP promoted OC formation and bone resorption and expression of OC-associated genes. CLP-induced bone loss was prevented by Zoledronic acid. At the molecular level, CLP inhibited the activity of the ubiquitin E3 ligase Itch. CLP did not promote OC formation from bone marrow cells of Itch-/- mice in vitro nor induce bone loss in Itch-/- mice. Our findings indicate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by Zoledronic acid. Thus, anti-resorptive therapy could be used to prevent bone loss in patients taking antidepressants, such as CLP.
基金：
National Institute of Health PHS awards (AR48697, AR63650 and AR69789
to L. Xing; 1S10RR027340 and AR43510 to B.F. Boyce, P30 AR061307 and P50 AR054041 to E.M. Schwarz)
and NYSTEM (CO-29548) to L. Xing. X. Li’s salary was partially supported by a grant from National Natural
Foundation of China (81202037 to Z. Wang). M. Wang was supported by the grant from National Natural
Foundation of China (81473451 to L. Pei).
第一作者机构：[1]Department of Immuno-oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China[2]Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642,USA
通讯作者：
通讯机构：[2]Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642,USA[4]Centerfor Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
推荐引用方式(GB/T 7714)：
Li Xing,Sun Wen,Li Jinbo,et al.Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid[J].SCIENTIFIC REPORTS.2017,7:doi:10.1038/srep41358.
APA：
Li, Xing,Sun, Wen,Li, Jinbo,Wang, Mengmeng,Zhang, Hengwei...&Xing, Lianping.(2017).Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid.SCIENTIFIC REPORTS,7,
MLA：
Li, Xing,et al."Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid".SCIENTIFIC REPORTS 7.(2017)
