Abstract
Background. Erzhi pill (EZP), a traditional Chinese herbal formula, has been widely used to treat postmenopausal osteoporosis (PMOP) in China. However, its molecular mechanisms remain unclear. The aim of the present study is to investigate the antiosteoporotic effect of EZP on an ovariectomized rat model of PMOP. We performed the biomarkers of bone metabolism disorder, bone morphology, bone mineral density (BMD), and bone biomechanics to confirm the successful establishment of the PMOP model. We then investigated the expression of biomarkers related to the Sirt1/Foxo axis. We also examined microRNA-132 (miR-132), a regulator in the Sirtuin1 (Sirt1) expression. The bone metabolism disorder, bone morphology, BMD, and bone biomechanics in ovariectomized rats were improved by EZP administration. The antiosteoporotic effect of EZP was confirmed. We also found that the expressions of Sirt1, Runx2, Foxo1, and Foxo3a were downregulated in ovariectomized rats, while being then upregulated by EZP administration. And the expression of PPAR-γ and miR-132 was upregulated in ovariectomized rats and then downregulated by EZP administration. These results provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be considered as a potential therapeutic target for PMOP in the future.
Highlights
Postmenopausal osteoporosis (PMOP) as a severe public health problem is a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue quite common in postmenopausal women [1,2,3]
The second finding was that we confirmed that the Sirt1/Foxo axis may play a role in the mechanisms of Erzhi pill (EZP) production, since we found the expressions of PPAR-γ and miR-132 downregulated, whereas the expressions of Sirt1, Runx2, Foxo1, and Foxo3a upregulated by EZP administration
We found that EZP can improve OPG, OPG/receptor activator of NFKB ligand (RANKL), bone alkaline phosphatase (BALP), bone mineral density (BMD), and Tb.Th which was suppressed by estrogen deficiency, and the biomechanical function reduction was suppressed
Summary
Postmenopausal osteoporosis (PMOP) as a severe public health problem is a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue quite common in postmenopausal women [1,2,3]. Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating Runx gene expression by the Sirt1/Foxo axis [8, 9], indicating that promotion of the Sirt1/Foxo axis might play a role in the mechanisms of some Chinese herbs. We found that the expressions of Sirt, Runx, Foxo, and Foxo3a were downregulated in ovariectomized rats, while being upregulated by EZP administration. The expression of PPAR-γ and miR-132 was upregulated in ovariectomized rats and downregulated by EZP administration. These results provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be considered as a potential therapeutic target for PMOP in the future
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