Protective effects of 2,3,5,4‐tetrahydroxystilbene‐2‐o‐β‐D‐glucoside against osteoporosis: Current knowledge and proposed mechanisms

Abstract

The aim of this study was to explore the mechanism underlying the protective effects of 2,3,5,4-tetrahydroxystilbene-2-o-β-D-glucoside (TSG) against osteoporosis. MC3T3-E1 mouse osteoblast precursor cells were used to analyze the protective effects of TSG on osteoblast apoptosis and differential inhibition induced by oxidative stress to determine the gene expression of forkhead transcription factor FKHRL1 (FoxO3a), T cell factors (TCFs), and downstream genes. A mouse model was used to assess the protective effects of TSG on ovariectomy-induced osteoporosis as well as on Cell Counting Kit-8 (CCK) gene expression, including that of FoxO3a. The mechanism underlying the protective effects of TSG against osteoporosis was further explored using high-throughput sequencing data. A CCK-8 assay in MC3T3-E1 cells and hematoxylin and eosin staining in mouse tissue indicated that cell viability and bone tissue development were inhibited by oxidative stress and ovariectomy and that TSG neutralized or attenuated this effect. The expression levels of FoxO3a, TCF, and downstream genes and the indices of oxidative stress were the same in MC3T3-E1 cells and the bone tissues of the mouse model. Bioinformatics analysis indicated that the cardiac muscle contraction and chemokine signaling pathway were disturbed in MC3T3-E1 cells treated with hydrogen peroxide. Gene ontology-biological process analysis revealed the influence of TSG treatment. Osteoporosis and cardiac diseases appear to share a common mechanism. In addition to Wnt/FoxO3a signaling, the immune system and the chemokine signaling pathway may contribute to the protective mechanism of TSG.