Abstract
Bone metabolism is a physiological process that involves both osteoblasts and osteoclasts. Pathological changes of osteoclasts are commonly seen in osteoporosis diseases. Juglanin is a natural compound, reported to have an inhibitory effect on inflammation, oxidative stress and cancer progression. The purpose of this study is to explore the role that Juglanin plays on the osteoclast functions and underlying signaling pathways. In vitro study demonstrated that Juglanin had negative influence on osteoclastic differentiation by suppressing the transcription activity of osteoclastogenesis-related genes and proteins. To determine the underlying mechanism, Western blot was employed to show that Juglanin could significantly have negative effect on the phosphorylation of P50, P65, I-κB， ultimately suppressing the expression and transcriptional activity of nuclear factor of activated T cells (NFATc1). In vivo Juglanin treatment attenuate bone reducing in mice with removed ovary through suppressing osteoclast functioning. Taken together, our study demonstrated that in the molecular mechanism, JUG inhibited the expression of receptor activator of nuclear factor-κ B ligand (RANKL) induced NF - κ B signaling pathway, thus may play a vital part in preventing postmenopausal osteoporosis.
Highlights
Osteoporosis is the disease with high incidence rate which is manifested by bone loss and bone microstructure reducing, resulting in impaired rigidity as well as increased risk of fracture (Ensrud and Crandall, 2017; Leutner et al, 2019)
RANK (NF-κB receptor activator) and its ligand RANKL initiate the signaling for osteoclast formation (Park et al, 2017; Choi et al, 2018; Funakubo et al, 2018; Ikebuchi et al, 2018), recruiting TNF receptor related factors 6 which further stimulate the phosphorylation of down-stream transcription factors (Sambandam et al, 2016; Wu et al, 2016; van Dam et al, 2019)
ALP assay and alizarin red staining assay showed that JUG (80 μmol/L) had no inhibitory or promotive effect on BMSCs differentiation (Supplementary Figures S1A,B)
Summary
Osteoporosis is the disease with high incidence rate which is manifested by bone loss and bone microstructure reducing, resulting in impaired rigidity as well as increased risk of fracture (Ensrud and Crandall, 2017; Leutner et al, 2019). Postmenopausal osteoporosis (PMO) is a typical orthopedic disease caused by excessive activation of osteoclasts (Ensrud and Crandall, 2019). It was observed that the osteoclastogeneis process was over-activated after menopause, leading to net bone loss and increased risk of osteoporosis (Levin et al, 2018; Kanis et al, 2019). It has been shown that selective inhibition of NF-κB and MAPK pathways can reduce osteoclast formation (Yao et al, 2017; Kim et al, 2018)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
