Experimental investigation of adipose-derived mesenchymal stem cell-derived exosomes in the treatment of osteoporosis via the hsa_circ_0028877/miR-4728-3p/PTCH1 axis

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-10-01 DOI:10.1016/j.intimp.2025.115625

Jianqiao Li, Qingsong Gu, Yiheng Li, Yifan Gu, Yuhu Chen, Linhui Wang, Ziru Wang, Yicong Wang, Min Yang

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引用次数: 0

Abstract

Background

hsa_circ_0028877 may serve as a biomarker for postmenopausal osteoporosis (PMOP) based on bioinformatics analysis; nevertheless, the underlying mechanism remains ambiguous. ADSCs-derived exosomes (ADSCs-exos), as an innovative cell-free therapeutic agent that influences numerous biological processes, including immunological modulation, reduction of oxidative damage, and enhancement of tissue repair and regeneration.

Objective

In vitro experiments were performed to evaluate the impact of hsa_circ_0028877 on cellular proliferation, osteogenic differentiation, and osteoclast differentiation. The study examined the regulatory function of ADSCs-exos on the hsa_circ_0028877/miR-4728-3p/PTCH1 axis and its therapeutic implications for osteoporosis.

Methods

The ovariectomised rat (OVX) model was employed to simulate PMOP. The impact of hsa_circ_0028877 overexpression and knockdown on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were examined. The RNA immunoprecipitation (RIP) method was employed to validate the connection among hsa_circ_0028877, miR-4728-3p, and PTCH1. ADSCs-exos modulate their downstream molecular pathway by obstructing the nuclear transport of hsa_circ_0028877. The impact of ADSCs-exos on bone mass, trabecular microstructure, and the mineralization capacity of BMSCs was evaluated in a rat model.

Results

hsa_circ_0028877 is significantly expressed in ovariectomised rat BMSCs. hsa_circ_0028877 enhances PTCH1 expression through its interaction with miR-4728-3p. ADSCs-exos can rehabilitate bone mass in the distal femur of ovariectomised rats. ADSCs-exos facilitate osteogenesis by obstructing the nuclear export of hsa_circ_0028877, significantly boosting trabecular microstructure and mineralization in the BMSCs of ovariectomised rats.

Conclusion

ADSCs-exos promote osteogenic differentiation and bone formation in BMSCs by obstructing the nuclear export of hsa_circ_0028877 and modulating the hsa_circ_0028877/miR-4728-3p/PTCH1 axis, thereby improving PMOP.

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脂肪来源的间充质干细胞来源的外泌体通过hsa_circ_0028877/miR-4728-3p/PTCH1轴治疗骨质疏松症的实验研究。

背景：基于生物信息学分析，hsa_circ_0028877可能作为绝经后骨质疏松症（PMOP）的生物标志物；然而，潜在的机制仍然不明确。adscs衍生外泌体（ADSCs-exos），作为一种创新的无细胞治疗剂，影响许多生物过程，包括免疫调节，减少氧化损伤，增强组织修复和再生。目的：通过体外实验研究hsa_circ_0028877对细胞增殖、成骨分化和破骨细胞分化的影响。该研究检测了ADSCs-exos对hsa_circ_0028877/miR-4728-3p/PTCH1轴的调控功能及其对骨质疏松症的治疗意义。方法：采用去卵巢大鼠（OVX）模型模拟PMOP。研究hsa_circ_0028877过表达和敲低对骨髓间充质干细胞成骨分化的影响。采用RNA免疫沉淀（RIP）方法验证hsa_circ_0028877、miR-4728-3p和PTCH1之间的联系。ADSCs-exos通过阻断hsa_circ_0028877的核转运来调节其下游分子通路。在大鼠模型中评估ADSCs-exos对骨量、骨小梁微观结构和BMSCs矿化能力的影响。结果：hsa_circ_0028877在去卵巢大鼠骨髓间充质干细胞中显著表达。hsa_circ_0028877通过与miR-4728-3p的相互作用增强PTCH1的表达。ADSCs-exos可修复去卵巢大鼠股骨远端骨量。ADSCs-exos通过阻碍hsa_circ_0028877的核输出促进成骨，显著提高去卵巢大鼠骨髓间质干细胞的小梁微观结构和矿化。结论：ADSCs-exos通过阻断hsa_circ_0028877的核输出，调节hsa_circ_0028877/miR-4728-3p/PTCH1轴，从而促进骨髓间质干细胞成骨分化和骨形成，从而改善PMOP。

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

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.