Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4/nuclear factor kappa B pathway by increasing miR-92b-3p expression
机构：[1]Department of Traditional Chinese Medicine, The Third People’s Hospital of Yunnan Province, Kunming, China[2]Department of Emergency Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院[3]Department of Orthopedics, Calmett Hospital & The First Hospital of Kunming, Kunming, China[4]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China[5]Normal Human Anatomy and Histological Embryology Department, Yunnan University of Traditional Chinese Medicine, Kunming, China[6]Department of Encephalopathy, Guangzhou Conghua Hospital of Traditional Chinese Medicine, Guangzhou, China
Introduction: Resveratrol (RES) exhibits estrogen-like effects and has potential applications to treatment of osteoporosis caused by estrogen deficiency; however, the specific mechanism of action of RES remains unclear. Here, we examined the therapeutic effects of RES on ovariectomized (OVX) rats with osteoporosis and determined the underlying mechanism. Methods: We established an OVX rat model to study osteoporosis caused by estrogen deficiency. The treatment groups were given orally with RES (50, 100, and 200 mg/day), the estrogen group received 0.8 mg/kg E2 daily via oral route, and the sham-operated and control groups received an equivalent dose of sodium carboxymethylcellulose orally. After 12 weeks of treatment, we used real-time quantitative polymerase chain reaction (PCR) and Western blot analysis to measure the gene and protein expression of miR-92b-3p, Nox4, NF-kappa Bp65, I kappa B, BMP2, Smad7, and RUNX-2 in bone tissues. Right femur structural parameters were evaluated by micro-CT. Dual-energy X-ray 4500 W was used to determine systemic bone mineral density (BMD). Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the serum levels of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), anti-tartrate acid phosphatase-5b (PTRA5b), and carboxylated terminal peptide (CTX-I). The rat femoral bone specimens were stained using hematoxylin and eosin for pathological examination Results: We observed increased levels of serum estrogen in both ovaries, elevated miR-92b-3p levels in bone tissues, reduced levels of Nox4, NF-kappa Bp65, p-I kappa B-a, and cathepsin K, and elevated gene and protein expression of BMP2, Smad7, and RUNX-2 in the OVX rat model of osteoporosis after treatment with RES. Elevated levels of BALP, OPG, ALP, and BMD along with reduced levels of TRAP-5b and CTX-I were also observed. The structural model index (SMI) and the trabecular space (Tb. Sp) decreased, while the trabecular thickness (Tb. Th), bone volume fraction (BV/TV), trabecular number (Tb.N), and tissue bone density (Conn.D) increased, thereby improving osteoporosis induced by estrogen deficiency in both ovaries. Conclusion: Cathepsin K expression and Nox4/NF-kappa B signaling pathway were suppressed by the elevated expression of miR-92b-3p. This inhibition was pivotal in the protective effect of RES against osteoporosis induced by estrogen deficiency in both ovaries. Thus, RES efficiently alleviated osteoporosis induced by estrogen deficiency in rats.
基金：
Yunnan Applied Basic Research Project-Union Foundation of China [2017FE468(-032), 2018FE001(-283)]
第一作者机构：[1]Department of Traditional Chinese Medicine, The Third People’s Hospital of Yunnan Province, Kunming, China[*1]Department of Traditional Chinese Medicine, The Third People’s Hospital of Yunnan Province, Kunming 650011, Yunnan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Traditional Chinese Medicine, The Third People’s Hospital of Yunnan Province, Kunming, China[*1]Department of Traditional Chinese Medicine, The Third People’s Hospital of Yunnan Province, Kunming 650011, Yunnan, China.
推荐引用方式(GB/T 7714)：
Zhang Ye,Liu Ming-wei,He Yun,et al.Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4/nuclear factor kappa B pathway by increasing miR-92b-3p expression[J].INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY.2020,34:doi:10.1177/2058738420941762.
APA：
Zhang, Ye,Liu, Ming-wei,He, Yun,Deng, Ning,Chen, Yan...&Xie, Wei.(2020).Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4/nuclear factor kappa B pathway by increasing miR-92b-3p expression.INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY,34,
MLA：
Zhang, Ye,et al."Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4/nuclear factor kappa B pathway by increasing miR-92b-3p expression".INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY 34.(2020)
