BMSC-derived exosomal CD73 mediated macrophage polarization promotes osteoblastic differentiation in diabetes

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-06-14 DOI:10.1016/j.yexcr.2025.114653

Yiping Dou , Shujia Yu , Shiyu Cao, Kang Gao, Menghao Lv, Yilin He, Ruihong Ma, Qian Zhu, Chenrui Li, Zhenhua Gao, Pan Ma

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Abstract

Stem cell-derived exosomes have exhibited promise for applications in tissue regeneration. However, the osteogenic ability of exosomes derived from bone marrow mesenchymal stem cells(BMSCs) in diabetes is impaired. Exosomes play a role in intercellular communication and affect the functional status of many adjacent cells. The micro-inflammatory state in diabetes often leads to a higher proportion of M1/M2 macrophages in the tissue damage area than in non-diabetic individuals, which is unfavorable for tissue regeneration and delays wound healing. In the present study, we compared the macrophage polarization effect of exosomes secreted by BMSCs derived from type 2 diabetic rats(Exo(dm)) and derived from normal rats(Exo(wis)). The impact of Exo(dm) on regulating the polarization to M2 type in macrophages was weaker than that of Exo(wis), which brought less osteogenesis and was one of the reasons for poor regenerative repair of bone defects. To go a step further, Exo(dm) has lower expression of CD73, which could activate adenosine receptor A2b and cAMP/AKP pathway, leading to disorder of macrophage polarization in diabetes.

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骨髓间充质干细胞衍生的外泌体CD73介导的巨噬细胞极化促进糖尿病成骨细胞分化。

干细胞衍生的外泌体在组织再生中具有广阔的应用前景。然而，来自骨髓间充质干细胞（BMSCs）的外泌体在糖尿病中的成骨能力受损。外泌体在细胞间通讯中发挥重要作用，并影响许多相邻细胞的功能状态。糖尿病患者的微炎症状态往往导致M1/M2巨噬细胞在组织损伤区域的比例高于非糖尿病患者，这不利于组织再生和延迟伤口愈合。在本研究中，我们比较了来自2型糖尿病大鼠（Exo(dm)）和来自正常大鼠（Exo(wis)）的骨髓间充质干细胞分泌的外泌体的巨噬细胞极化效应。Exo（dm）对巨噬细胞向M2型极化的调节作用弱于Exo(wis)，导致成骨较少，是骨缺损再生修复较差的原因之一。进一步说，Exo（dm）中CD73的表达较低，CD73可以激活腺苷受体A2b和cAMP/AKP通路，导致糖尿病巨噬细胞极化紊乱。

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

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.