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High follicle-stimulating hormone levels accelerate cartilage damage of knee osteoarthritis in postmenopausal women through the PI3K/AKT/NF-κB pathway.
FEBS Open Bio ( IF 2.6 ) Pub Date : 2020-09-10 , DOI: 10.1002/2211-5463.12975
Yaping Liu 1, 2, 3, 4 , Mengqi Zhang 1, 2, 3 , Dehuan Kong 5 , Yan Wang 1, 2, 3 , Jian Li 6 , Wenjuan Liu 7 , Yilin Fu 1, 2, 3 , Jin Xu 1, 2, 3, 8
Affiliation  

Osteoarthritis is the main cause of pain and disability in the elderly, with the most commonly affected joint being the knee. The prevalence of knee osteoarthritis (KOA) is significantly increased in postmenopausal women, although the mechanisms underlying KOA remain unclear. The present study aimed to investigate the association between follicle‐stimulating hormone (FSH) and postmenopausal women with KOA aged between 50 and > 70 years, as well as explore its underlying molecular mechanisms. Here, we report that the 50–60 years age group had the highest level of serum FSH. Compared to the low FSH group (< 40 mIU·mL−1) in the same age group, the high FSH group (> 40 mIU·mL−1) showed more severe cartilage damage. Furthermore, phosphorylated (p)‐phosphoinositide 3‐kinase (PI3K)/PI3K, p‐AKT/AKT and p‐nuclear factor kappa B (NF‐κB)/NF‐κB levels were significantly higher in the high FSH group compared to the low FSH group. Immunofluorescence experiments showed that FSH stimulation promoted the translocation of NF‐κB p65 into the nucleus, and decreased type II collagen and aggrecan in ATDC5 cells. Moreover, we used western blotting in ATDC5 cells to demonstrate that FSH decreased type II collagen and increased p‐PI3K/PI3K, p‐AKT/AKT, p‐NF‐κB/NF‐κB and p‐IKB/IKB in a concentration‐dependent manner. Our results suggest that increased FSH levels are associated with KOA for postmenopausal women aged 50–60 years and that high FSH levels might damage the cartilage tissues through the PI3K/AKT/NF‐κB pathway.

中文翻译:

高促卵泡激素水平通过 PI3K/AKT/NF-κB 通路加速绝经后妇女膝骨关节炎的软骨损伤。

骨关节炎是老年人疼痛和残疾的主要原因,最常受影响的关节是膝关节。膝骨关节炎 (KOA) 的患病率在绝经后妇女中显着增加,尽管 KOA 的潜在机制仍不清楚。本研究旨在调查促卵泡激素 (FSH) 与 50 至 70 岁绝经后女性 KOA 之间的关系,并探讨其潜在的分子机制。在这里,我们报告了 50-60 岁年龄组的血清 FSH 水平最高。与同年龄组的低FSH组(< 40 mIU·mL -1 )相比,高FSH组(> 40 mIU·mL -1) 表现出更严重的软骨损伤。此外,与高 FSH 组相比,高 FSH 组的磷酸化 (p)-磷酸肌醇 3-激酶 (PI3K)/PI3K、p-AKT/AKT 和 p-核因子 kappa B (NF-κB)/NF-κB 水平显着升高。低FSH组。免疫荧光实验表明,FSH 刺激促进 NF-κB p65 易位进入细胞核,并减少 ATDC5 细胞中的 II 型胶原蛋白和聚集蛋白聚糖。此外,我们在 ATDC5 细胞中使用蛋白质印迹法证明 FSH 降低 II 型胶原蛋白并增加 p-PI3K/PI3K、p-AKT/AKT、p-NF-κB/NF-κB 和 p-IKB/IKB 浓度 -依赖的方式。我们的研究结果表明,FSH 水平升高与 50-60 岁绝经后妇女的 KOA 相关,高 FSH 水平可能通过 PI3K/AKT/NF-κB 通路损伤软骨组织。
更新日期:2020-10-02
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