淫羊藿苷通过激活自噬产生抗衰老作用从而实现骨质疏松症缓解。
Osteoporosis remission via an anti-inflammaging effect by icariin activated autophagy.
作者信息
Bai Long, Liu Yanpeng, Zhang Xiaohui, Chen Peiru, Hang Ruiqiang, Xiao Yin, Wang Jing, Liu Changsheng
机构信息
Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China; Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China.
Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China; The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China.
出版信息
Biomaterials. 2023 Jun;297:122125. doi: 10.1016/j.biomaterials.2023.122125. Epub 2023 Apr 10.
The pace of bone formation slows down with aging, which leads to the development of osteoporosis. In addition to senescent bone marrow mesenchymal stem cells (S-BMSCs), senescent macrophages (S-MΦs) present in the bone marrow produce numerous inflammatory cytokines that contribute to the inflammaged microenvironment and are involved in the development of osteoporosis. Although autophagy activation has shown a significant anti-aging effect, its influence on inflammaging and its role in osteoporosis treatment remain unclear. Traditional Chinese herbal medicine contains bioactive components that exhibit remarkable advantages in bone regeneration. We have demonstrated that icariin (ICA), a bioactive component of traditional Chinese herbal medicine, activates autophagy, exerts a significant anti-inflammaging effect on S-MΦs, and rejuvenates osteogenesis of S-BMSCs, thereby alleviating bone loss in osteoporotic mice. The transcriptomic analysis further reveals that the TNF-α signaling pathway, which is significantly associated with the level of autophagy, regulates this effect. Moreover, the expression of senescence-associated secretory phenotype (SASP) is significantly reduced after ICA treatment. In summary, our findings suggest that bioactive components/materials targeting autophagy can effectively modulate the inflammaging of S-MΦs, offering an innovative treatment strategy for osteoporosis remission and various age-related comorbidities.
随着年龄增长，骨形成速度减缓，这会导致骨质疏松症的发生。除了衰老的骨髓间充质干细胞（S-BMSCs）外，骨髓中存在的衰老巨噬细胞（S-MΦs）会产生大量炎性细胞因子，这些因子会促成炎性衰老微环境并参与骨质疏松症的发展。尽管自噬激活已显示出显著的抗衰老作用，但其对炎性衰老的影响及其在骨质疏松症治疗中的作用仍不清楚。传统中草药含有在骨再生方面具有显著优势的生物活性成分。我们已经证明，淫羊藿苷（ICA），一种传统中草药的生物活性成分，可激活自噬，对S-MΦs发挥显著的抗炎性衰老作用，并使S-BMSCs的成骨功能恢复活力，从而减轻骨质疏松症小鼠的骨质流失。转录组分析进一步揭示，与自噬水平显著相关的肿瘤坏死因子-α信号通路调节了这一作用。此外，ICA处理后衰老相关分泌表型（SASP）的表达显著降低。总之，我们的研究结果表明，靶向自噬的生物活性成分/物质可以有效调节S-MΦs的炎性衰老，为缓解骨质疏松症及各种与年龄相关的合并症提供了一种创新的治疗策略。
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