Peng Wei, Zhang Wenjuan, Wu Qici, Cai Shunyou, Jia Tingting, Sun Jiarui, Lin Zhichao, Alitongbieke Gulimiran, Chen Yixuan, Su Yi, Lin Jinmei, Cai Lisheng, Sun Yuqin, Pan Yutian, Xue Yu
The Engineering Technological Center of Mushroom Industry, Minnan Normal University, Zhangzhou, Fujian 363000, China.
Fujian Fungal Active Substance Engineering Technology Center, Zhangzhou, Fujian 363000, China.
J Nat Prod. 2021 Apr 23;84(4):1294-1305. doi: 10.1021/acs.jnatprod.1c00002. Epub 2021 Feb 26.
Glucosamine hydrochloride (GAH), one of the most basic and important derivatives of chitin, is obtained by hydrolysis of chitin in concentrated hydrochloric acid. At present, little is known about how GAH functions in skeletal development. In this report, we demonstrate that GAH, extracted from the cell wall of , acts in a dose-dependent manner to promote not only cartilage and bone development in larvae but also caudal fin regeneration in adult fish. Furthermore, GAH treatment causes a significant increase in expression of bone-related marker genes, indicating its important role in promoting skeletal development. We show that in both larval and adult osteoporosis models induced by high iron osteogenic defects are significantly ameliorated after treatment with GAH, which regulates expression of a series of bone-related genes. Finally, we demonstrate that GAH promotes skeletal development and injury repair through bone morphogenetic protein (Bmp) signaling, and it works at the downstream of the receptor level. Taken together, our findings not only provide a strong research foundation and strategy for the screening of natural osteoporosis drugs and product development using a zebrafish model but also establish the potential for the development of -derived GAH as a new drug for osteoporosis treatment.
盐酸氨基葡萄糖(GAH)是几丁质最基本且最重要的衍生物之一,它通过在浓盐酸中水解几丁质获得。目前,关于GAH在骨骼发育中的作用知之甚少。在本报告中,我们证明从[未提及的来源]细胞壁提取的GAH以剂量依赖的方式发挥作用,不仅能促进幼虫的软骨和骨骼发育,还能促进成年鱼的尾鳍再生。此外,GAH处理导致骨相关标记基因的表达显著增加,表明其在促进骨骼发育中的重要作用。我们表明,在高铁诱导的幼虫和成年骨质疏松模型中,GAH处理后成骨缺陷均得到显著改善,GAH可调节一系列骨相关基因的表达。最后,我们证明GAH通过骨形态发生蛋白(Bmp)信号促进骨骼发育和损伤修复,且在受体水平的下游起作用。综上所述,我们的研究结果不仅为利用斑马鱼模型筛选天然骨质疏松药物和产品开发提供了坚实的研究基础和策略,还确立了将[未提及的来源]衍生的GAH开发为骨质疏松治疗新药的潜力。