Rhizoma Drynariae-derived EV-like particles alleviate osteoporosis by promoting osteogenic differentiation in BMSCs through the activation of the hsa_circ_0001275/miR-422a pathway

IF 3.5 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-04-14 DOI:10.1016/j.bone.2025.117489

Jiawen Shen , Yuzhen Chen , Mingyue Pan , Sirui Zhou , Yukun Xu , Fubin Liu , Tianxin Qiu , Dongxiao Li , Qing Zhao , Kewei Zhao

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引用次数: 0

Abstract

Background

Osteoporosis (OP) is the most prevailing primary bone disease caused by the imbalance between bone resorption and formation. Rhizoma Drynariae-derived EV-like particles (RD-EVLP) perform the anti-osteoporosis effect by promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells (h-BMSCs) which may be regulated by circular RNAs (circRNAs) and microRNAs (miRNAs). This study aimed to reveal the functional roles and mechanisms of the RD-EVLP regulating osteogenic differentiation of osteoporosis through the activation of hsa_circ_0001275 sponging miR-422a.

Results

Notably, RD-EVLP isolated from fresh Rhizoma Drynariae via differential ultracentrifugation demonstrated three critical pharmacological attributes: (1) excellent biosafety profile with non-toxic and gastrointestinal stability, (2) bone-targeting specificity evidenced by femoral accumulation, and (3) potent anti-osteoporotic effects through promoting osteogenic differentiation in vivo. Meanwhile, RD-EVLP effectively internalized by h-BMSCs, enhanced proliferation of h-BMSCs, and promoted osteogenic differentiation and bone formation in vitro. For another, hsa_circ_0001275 and insulin like growth factor 1 receptor (IGF1R) expressions were upregulated while miR-422a expression was downregulated during osteogenic differentiation. Knockdown of hsa_circ_0001275 inhibited mineralized nodule formation. Moreover, miR-422a was a target of hsa_circ_0001275 and knockdown of miR-422a promoted mineralized nodule formation and greatly reinforced the expression of runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), osteocalcin (OCN). What's more, miR-422a suppressed h-BMSCs osteogenic differentiation by downregulating IGF1R. Finally, RD-EVLP promoted osteogenic differentiation by enhancing hsa_circ_0001275 and IGF1R while reducing miR-422a expression levels of h-BMSCs during osteogenic induction.

Conclusion

hsa_circ_0001275 could promote osteogenic differentiation by sponging miR-422a to upregulate IGF1R expression and RD-EVLP performed anti-OP activity through hsa_circ_0001275/miR-422a pathway.

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干连衍生的ev样颗粒通过激活hsa_circ_0001275/miR-422a通路促进BMSCs的成骨分化，从而缓解骨质疏松症

背景骨质疏松症（OP）是由骨吸收和骨形成失衡引起的最常见的原发性骨病。黄连衍生ev -样颗粒（RD-EVLP）通过促进人骨髓间充质干细胞（h-BMSCs）的成骨分化而发挥抗骨质疏松作用，这种分化可能受环状rna （circRNAs）和microRNAs （miRNAs）的调控。本研究旨在通过激活hsa_circ_0001275海绵miR-422a，揭示RD-EVLP调控骨质疏松成骨分化的功能作用及机制。结果通过鉴别超离心从新鲜干连中分离得到的RD-EVLP具有三个重要的药理学特性：(1)具有良好的生物安全性，无毒且胃肠道稳定；(2)具有股骨蓄积的骨靶向特异性；(3)通过促进体内成骨分化而具有有效的抗骨质疏松作用。同时，RD-EVLP被h-BMSCs有效内化，增强h-BMSCs的增殖，促进体外成骨分化和骨形成。另一方面，在成骨分化过程中，hsa_circ_0001275和胰岛素样生长因子1受体（IGF1R）表达上调，而miR-422a表达下调。敲除hsa_circ_0001275抑制矿化结核的形成。此外，miR-422a是hsa_circ_0001275的靶点，miR-422a的敲低促进矿化结节的形成，并大大增强了矮子相关转录因子2 （RUNX2）、骨形态发生蛋白2 （BMP2）、骨钙素（OCN）的表达。此外，miR-422a通过下调IGF1R抑制h-BMSCs成骨分化。最后，RD-EVLP通过增强hsa_circ_0001275和IGF1R促进成骨分化，同时降低成骨诱导过程中h-BMSCs的miR-422a表达水平。结论hsa_circ_0001275可通过海绵作用miR-422a上调IGF1R表达促进成骨分化，RD-EVLP可通过hsa_circ_0001275/miR-422a通路发挥抗op活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bone 医学-内分泌学与代谢

CiteScore

8.90

自引率

4.90%

发文量

264

审稿时长

30 days

期刊介绍： BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.