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海藻糖通过促进自噬减轻成骨细胞焦亡,从而挽救卵巢切除诱导的绝经后骨质疏松症。

Trehalose Rescues Postmenopausal Osteoporosis Induced by Ovariectomy through Alleviating Osteoblast Pyroptosis via Promoting Autophagy.

作者信息

Hu Xinli, Wang Wei, Chen Xiaolong, Kong Chao, Zhao Xuan, Wang Zheng, Zhang Haojie, Lu Shibao

机构信息

Department of Orthopedics, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.

National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.

出版信息

Biomedicines. 2024 Sep 29;12(10):2224. doi: 10.3390/biomedicines12102224.

Abstract

BACKGROUND

Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone mass recovery in ovariectomized rats and its underlying mechanisms remains unclear. In this study, trehalose was administered to ovariectomized rats to evaluate its therapeutic potential for osteoporosis following ovariectomy.

METHODS

Micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) and immunohistochemical staining techniques were utilized to evaluate the impact of trehalose on osteoporosis induced by ovariectomy (OVX) in mice, both in imaging and histological dimensions. Furthermore, the influence of trehalose on osteoblastogenesis and functional activity was quantified through Alizarin Red S (ARS) staining and immunoblotting assays.

RESULTS

Trehalose effectively mitigated bone loss, elevated autophagy and suppressed pyroptosis in ovariectomized rats. Furthermore, 3-methyladenine diminished the protective effects of trehalose, particularly in promoting autophagy and inhibiting pyroptosis.

CONCLUSIONS

Trehalose demonstrates significant potential in treating osteoporosis by suppressing NLRP3 inflammasome-driven pyroptosis, primarily through autophagy promotion. This suggests that trehalose could be a promising, safer alternative treatment for osteoporosis.

摘要

背景

骨质疏松症是一种常见的骨代谢疾病,通常需要长期药物治疗,而这可能会导致严重的副作用。海藻糖是一种在多种生物中发现的天然二糖,已被证明对自噬有促进作用。然而,海藻糖是否能改善去卵巢大鼠的骨量恢复及其潜在机制仍不清楚。在本研究中,对去卵巢大鼠给予海藻糖,以评估其对去卵巢后骨质疏松症的治疗潜力。

方法

利用微计算机断层扫描(Micro-CT)、苏木精-伊红(HE)染色和免疫组化染色技术,从影像学和组织学层面评估海藻糖对小鼠去卵巢(OVX)诱导的骨质疏松症的影响。此外,通过茜素红S(ARS)染色和免疫印迹分析定量海藻糖对成骨细胞生成和功能活性的影响。

结果

海藻糖有效减轻了去卵巢大鼠的骨质流失,提高了自噬水平,并抑制了细胞焦亡。此外,3-甲基腺嘌呤减弱了海藻糖的保护作用,特别是在促进自噬和抑制细胞焦亡方面。

结论

海藻糖在治疗骨质疏松症方面显示出显著潜力,主要通过促进自噬来抑制NLRP3炎性小体驱动的细胞焦亡。这表明海藻糖可能是一种有前景、更安全的骨质疏松症替代治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54e/11505409/bcc4d53aa850/biomedicines-12-02224-g001.jpg

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