Antidepressant duloxetine hydrochloride protects against ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation

抗抑郁药盐酸度洛西汀通过抑制破骨细胞分化防止小鼠卵巢切除引起的骨质流失

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作者:Weijun Zhou, Wenyun Zhou, Yonghao Bi, Zibin Zhou, Zhigao Zhou, Shaozhe Chen, Gang Xie, Zhen Lian, Guixin Yuan, Guanfeng Yao

Background

Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be elucidated whether these associations are related to exposure to antidepressants, a consequence of a disease process, or a combination of both.

Conclusion

The findings from this study suggest that DH, instead of causing bone mass loss, may assist in alleviating postmenopausal osteoporosis. These results can serve as a reference for the clinical treatment of patients with perimenopausal or postmenopausal depression using antidepressants.

Methods

This study investigates the independent effect of the antidepressant duloxetine hydrochloride (DH) on ovariectomy-induced bone loss in mice. One week after ovariectomy, the treated mice received DH. To explore the mechanism underlying the rescue of bone loss, bone marrow cells were isolated from mouse femurs and tibias, and macrophages extracted from them were induced to become osteoclasts in vitro while being treated with DH. Subsequently, the osteoclasts underwent Bulk RNA-Seq to reveal the involved signaling pathways. The

Results

The in vivo experiments demonstrated that DH treatment compromised ovariectomy-induced bone loss after 7 weeks. The in vitro experiments suggested that DH treatment attenuated osteoclast differentiation via the MAPKs/NFATc1 signaling pathway.

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