Evaluation of proanthocyanidins in treating Type 2 diabetic osteoporosis via SIRT6/Nrf2/GPX4 pathways

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

The FASEB Journal Pub Date : 2025-04-03 DOI:10.1096/fj.202403032R

Run-xun Ma, Bing-hao Lin, Si-xiang Feng, Yi-tian Bu, Zi-Hao Chen, Yi-xun Huang, En-Li Li, She-ji Weng, Lei Yang

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Abstract

This study investigates the therapeutic potential of proanthocyanidins (PAC) in addressing Type 2 diabetic osteoporosis (T2DOP) by activating the SIRT6/Nrf2/GPX4 signaling pathways. T2DOP is characterized by compromised bone structure and heightened oxidative stress, where ferroptosis plays a pivotal role. Utilizing a T2DOP mouse model and MC3T3-E1 cells under high glucose conditions, we evaluated the impact of PAC on bone health and iron homeostasis. Our results, obtained through micro-CT, histological staining, Western blot, and immunofluorescence analyses, revealed reductions in bone density and decreased GPX4 expression in T2DOP conditions, indicating ferroptosis and oxidative stress. However, PAC treatment improved trabecular bone structure, reduced bone marrow adipocytes, decreased oxidative stress, and enhanced expression of key osteogenic proteins. These findings highlight PAC's potential in mitigating T2DOP through the SIRT6/Nrf2/GPX4 pathways, offering promising therapeutic insights for managing diabetic osteoporosis.

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来源期刊

The FASEB Journal 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

6243

审稿时长

3 months

期刊介绍： The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.