Open AccessSchisandrin A restrains osteoclastogenesis by inhibiting reactive oxygen species and activating Nrf2 signalling
Author(s) -
Ni Shuo,
Qian Zhi,
Yuan Yin,
Li Dejian,
Zhong Zeyuan,
Ghorbani Farnaz,
Zhang Xu,
Zhang Fangxue,
Zhang Zhenhua,
Liu Zichen,
Yu Baoqing
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12882
Subject(s) - rankl , osteoclast , reactive oxygen species , chemistry , activator (genetics) , microbiology and biotechnology , in vivo , nf κb , receptor , pharmacology , signal transduction , biochemistry , biology
Objectives Intracellular reactive oxygen species (ROS) induced by receptor activator of NF‐kB ligand (RANKL) has been proven to be a critical factor in the development of osteoclasts. This study aimed to prove that schisandrin A (Sch), a novel anti‐oxidant compound, is able to suppress osteoclastogenesis and prevent bone loss in ovariectomized (OVX) mice by suppressing ROS via nuclear factor erythroid 2‐related factor (Nrf2). Material and Methods Micro‐CT was used to detect bone formation. The effects of Sch on receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced reactive oxygen species (ROS) were measured by dihydroethidium (DHE) staining in vivo and 2',7'‐dichlorodihydrofluorescein diacetate (DCFH‐DA) staining in vitro. Immunofluorescence staining was used to detect the expression of Nrf2 in vivo. siRNA was used to evaluate the effect of Nrf2 in osteoclastogenesis. Results Sch suppresses RANKL‐induced ROS production by regulating nuclear factor erythroid 2‐related factor (Nrf2) in vitro and vivo. Mechanistically, Sch enhances the expression of Nrf2 by regulating the degradation of Nrf2. Further, Sch suppresses phosphorylation of P65 and its nuclear translocation, as well as the degradation of IκBα. Collectively, our findings reveal that Sch protects against OVX‐induced bone loss by suppressing ROS via Nrf2. Conclusions Our results showed the potential of anti‐oxidant compound schisandrin A in the treatment of osteoporosis, highlighting Nrf2 as a novel promising target in osteoclast‐related disease.