Xu Lili, Shen Liyan, Yu Xiaolong, Li Peng, Wang Qing, Li Chengqian
Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Exp Ther Med. 2020 Feb;19(2):1084-1090. doi: 10.3892/etm.2019.8313. Epub 2019 Dec 10.
The nuclear factor E2-related factor 2 (Nrf2)/NLR family, pyrin domain containing protein 3 (NLRP3) plays an important role in osteoporosis (OP), so the effects of irisin on postmenopausal OP rats and osteoblast apoptosis through Nrf2/NLRP3 were explored in the present study. A total of 45 specific pathogen-free Sprague-Dawley rats were selected and divided into OP model group (OP group, n=15), 1 mmol/l irisin treatment group (irisin group, n=15) and normal control group (control group, n=15). After the trial period, the content of serum ALP was detected, the levels of tumor necrosis factor-α (TNF-α) in the serum and bone tissues were observed via ELISA, and the bone microstructure was observed via CT. Osteoblast apoptosis was determined through TUNEL assay, the content of apoptosis genes caspase-3 and Bcl-2, and key genes in Runt-related transcription factor 2 (Runx2), osteocalcin (OC), Nrf2 and NLRP3 was detected via RT-PCR. The protein expression of Bcl-2, Nrf2 and NLRP3 was determined via western blotting. The serum ALP level was increased in OP group compared with that in control group (P<0.05), while it declined in the irisin group. The content of TNF-α and interleukin-6 (IL-6) was significantly higher in OP group, while the content in the irisin group was close to that in the control group. The trabecular thickness, number and bone mineral density in the irisin group were all obviously larger and higher, respectively, than those in the OP group. The mRNA expression of Runx2, OC, Bcl-2 and Nrf2 in the irisin group were obviously higher (P<0.05), while that of caspase-3 and NLRP3 showed the opposite trends. The protein expression of Bcl-2 and Nrf2 in the irisin group was remarkably higher than those in the OP group, while that of NLRP3 was the opposite. irisin can upregulate Nrf2, inhibit NLRP3 inflammasome and lower the content of inflammatory factors, thereby suppressing osteoblast apoptosis in postmenopausal OP rats and reducing the incidence of postmenopausal OP.
核因子E2相关因子2（Nrf2）/NLR家族含pyrin结构域蛋白3（NLRP3）在骨质疏松症（OP）中起重要作用，因此本研究探讨了鸢尾素通过Nrf2/NLRP3对绝经后OP大鼠和成骨细胞凋亡的影响。共选取45只无特定病原体的Sprague-Dawley大鼠，分为OP模型组（OP组，n = 15）、1 mmol/l鸢尾素治疗组（鸢尾素组，n = 15）和正常对照组（对照组，n = 15）。试验期结束后，检测血清碱性磷酸酶（ALP）含量，采用酶联免疫吸附测定法（ELISA）观察血清和骨组织中肿瘤坏死因子-α（TNF-α）水平，通过CT观察骨微结构。采用末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL法）检测成骨细胞凋亡，通过逆转录-聚合酶链反应（RT-PCR）检测凋亡相关基因半胱天冬酶-3（caspase-3）和Bcl-2以及核心结合因子2（Runx2）、骨钙素（OC）、Nrf2和NLRP3的关键基因含量。通过蛋白质印迹法检测Bcl-2、Nrf2和NLRP3的蛋白表达。与对照组相比，OP组血清ALP水平升高（P<0.05），而鸢尾素组血清ALP水平下降。OP组TNF-α和白细胞介素-6（IL-6）含量显著升高，而鸢尾素组含量接近对照组。鸢尾素组的骨小梁厚度、数量和骨密度分别明显大于和高于OP组。鸢尾素组Runx2、OC、Bcl-2和Nrf2的mRNA表达明显升高（P<0.05），而caspase-3和NLRP3的mRNA表达呈相反趋势。鸢尾素组Bcl-2和Nrf2的蛋白表达明显高于OP组，而NLRP3的蛋白表达则相反。鸢尾素可上调Nrf2，抑制NLRP3炎性小体并降低炎性因子含量，从而抑制绝经后OP大鼠成骨细胞凋亡并降低绝经后OP的发生率。
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