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Ajugol上调TFEB介导的自噬可减轻软骨细胞内质网应激并延缓小鼠模型骨关节炎进展。

Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model.

作者信息

Wu Jingtao, Yu Heng, Jin Yangcan, Wang Jingquan, Zhou Liwen, Cheng Teng, Zhang Zhao, Lin Binghao, Miao Jiansen, Lin Zhongke

机构信息

Department of Orthopaedics, Wenzhou Key Laboratory of Perinatal Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.

Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, Zhejiang Province, China.

出版信息

Chin Med. 2023 Sep 7;18(1):113. doi: 10.1186/s13020-023-00824-7.

DOI:10.1186/s13020-023-00824-7
PMID:37679844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10483732/
Abstract

BACKGROUND

Osteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA.

METHODS

We employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.

RESULTS

Our findings revealed that treatment with 50 μM Ajugol activated TFEB-mediated autophagy, alleviating ER stress-induced chondrocyte apoptosis and ECM degradation caused by TBHP. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.

CONCLUSION

These results provide compelling biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA by activating autophagy and attenuating ER stress-induced cell death and ECM degradation. The promising in vivo results further suggest the potential of Ajugol as a treatment strategy for OA progression.

摘要

背景

骨关节炎(OA)是一种在全球范围内高发的退行性疾病,其特征在于细胞外基质(ECM)的降解和软骨细胞的凋亡。紫背金盘醇,一种从地黄中提取的提取物,尚未对其调节OA发展的潜力进行研究。

方法

我们采用蛋白质免疫印迹法、免疫荧光法、免疫组织化学法、X射线成像、苏木精-伊红染色和番红O染色等技术,为紫背金盘醇作为调节OA的潜在治疗药物的作用提供生物学证据。此外,在一项体内实验中,腹腔注射50mg/kg紫背金盘醇可有效减轻内侧半月板不稳定(DMM)手术后OA的进展。

结果

我们的研究结果表明,用50μM紫背金盘醇处理可激活TFEB介导的自噬,减轻叔丁基过氧化氢(TBHP)诱导的内质网应激(ER)所致的软骨细胞凋亡和ECM降解。此外,在一项体内实验中,腹腔注射50mg/kg紫背金盘醇可有效减轻内侧半月板不稳定(DMM)手术后OA的进展。

结论

这些结果提供了令人信服的生物学证据,支持紫背金盘醇通过激活自噬和减轻ER应激诱导的细胞死亡及ECM降解来调节OA的潜在治疗药物作用。体内实验的良好结果进一步表明紫背金盘醇作为OA进展治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/056ad604cb67/13020_2023_824_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/87a348f10755/13020_2023_824_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/5fe75b5b4d65/13020_2023_824_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/df8e990ffe3f/13020_2023_824_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/056ad604cb67/13020_2023_824_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/f7a47c3ac655/13020_2023_824_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/c02e6ab430fd/13020_2023_824_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/c9d1f68b72ad/13020_2023_824_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/87a348f10755/13020_2023_824_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/5fe75b5b4d65/13020_2023_824_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/262e6a0d1bc4/13020_2023_824_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/df8e990ffe3f/13020_2023_824_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/10483732/056ad604cb67/13020_2023_824_Fig8_HTML.jpg

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