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牙髓干细胞来源的外泌体miR-31通过靶向mTOR增强软骨细胞自噬水平在骨关节炎治疗中的作用及潜在机制

The role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels.

作者信息

Zhao Guanglei, Lyu Jinyang, Huang Xin, Huang Gangyong, Chen Feiyan, Wei Yibing, Wang Siqun, Xia Jun, Chen Jie, Shi Jingsheng

机构信息

Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Arch Med Sci. 2023 Jan 14;20(5):1680-1694. doi: 10.5114/aoms/157032. eCollection 2024.

Abstract

INTRODUCTION

Osteoarthritis is the most prevalent progressive musculoskeletal disease. It leads to functional impairment and decreased quality of life. However, the current treatments remain unsatisfactory. Recent studies have revealed that exosomes derived from mesenchymal stem cells offer a promising approach to improve the pathological changes in osteoarthritis, cartilage tissue, and chondrocyte homeostasis.

MATERIAL AND METHODS

In this and study, we studied the effects and mechanisms of dental pulp stem cell-derived exosomes (DPSC-exosomes) on osteoarthritis in a mouse model.

RESULTS

The study findings showed that a dental pulp stem cell could generate typical characteristic exosomes. The injection of DPSC-exosomes ameliorated destruction of cartilage, promoted matrix synthesis, inhibited cell apoptosis, and decreased the expression of catabolic factors. However, this effect was shown to be almost eliminated when miR-31 antagomir was injected.

CONCLUSIONS

Furthermore, DPSC-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSC-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSC-exosomes have a chondroprotective role in a mouse osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.

摘要

引言

骨关节炎是最常见的进行性肌肉骨骼疾病。它会导致功能障碍和生活质量下降。然而,目前的治疗方法仍不尽人意。最近的研究表明,间充质干细胞来源的外泌体为改善骨关节炎、软骨组织和软骨细胞内环境稳定的病理变化提供了一种有前景的方法。

材料与方法

在本研究中,我们研究了牙髓干细胞来源的外泌体(DPSC-外泌体)对小鼠骨关节炎模型的影响及其机制。

结果

研究结果表明,牙髓干细胞能够产生具有典型特征的外泌体。注射DPSC-外泌体可改善软骨破坏,促进基质合成,抑制细胞凋亡,并降低分解代谢因子的表达。然而,当注射miR-31拮抗剂时,这种作用几乎消失。

结论

此外,DPSC-外泌体除了降低mTOR荧光素酶活性外,还显示出通过抑制mTOR促进软骨细胞自噬的能力。抑制miR-31后,DPSC-外泌体部分调节自噬的能力被阻断。简而言之,DPSC-外泌体在小鼠骨关节炎模型中具有软骨保护作用。其潜在机制可能与miR-31介导的mTOR-自噬途径抑制有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2856/11623167/fed87594bb08/AMS-20-5-157032-g001.jpg

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