Glycyrrhizin improves bone metabolism in ovariectomized mice via inactivating NF-κB signaling

• Published in: Climacteric : the journal of the International Menopause Society 2021-06, Vol.24 (3), p.253-260
• Main Authors: Tang, Y., Lv, X. L., Bao, Y. Z., Wang, J. R.
• Format: Article
• Language: English
• Subjects: Gene expression; glycyrrhizin; Menopause; Metabolism; NF-κB; Osteoporosis; Ovariectomized mice; postmenopausal osteoporosis
• ISSN: 1369-7137; 1473-0804
• DOI: 10.1080/13697137.2020.1828853

Postmenopausal osteoporosis (PMO) is a prevalent metabolic bone disease with high morbidity and serious complications. Here, we studied the effect of glycyrrhizin on bone metabolism using the ovariectomized (OVX) mouse model. Osteoclast-related gene expression and osteoclastic function were evaluated in RAW264.7 cells and bone marrow-derived monocytes (BMMs) by real-time polymerase chain reaction and bone resorption assay. For animal studies, female C57BL/6J mice were randomly divided into sham operated, OVX and OVX with glycyrrhizin groups. Bone mass and trabecular microarchitecture were analyzed by micro-computed tomography, dual X-ray absorptiometry, and histomorphometric analysis. Receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclastogenesis and the NF-κB signaling pathway were studied by tartrate-resistant acid phosphatase staining and western blotting, respectively. Glycyrrhizin inhibits RANKL-induced expression of Nfatc-1, c-Fos, Trap, Ds-stamp, and Ctsk in RAW264.7 cells. Also, fewer bone resorption pits form when BMMs are incubated in the presence of glycyrrhizin. Glycyrrhizin ameliorates bone loss and improves trabecular bone parameters in OVX mice. BMMs isolated from OVX mice show higher ability of RANKL-induced osteoclastogenesis, which is tremendously reversed by glycyrrhizin. There is significantly higher phosphorylation of IκB-α at Ser32 and NF-κB p65 at Ser536, as well as increased protein levels of c-FOS and NFATc-1 in BMMs of OVX mice, which are all greatly suppressed by glycyrrhizin. Our findings imply that glycyrrhizin is a potential efficient adjuvant therapeutic for PMO.