Bone marrow macrophage M2 polarization and adipose-derived stem cells osteogenic differentiation synergistically promote rehabilitation of bone damage
Bone marrow macrophage M2 polarization and adipose-derived stem cells osteogenic differentiation synergistically promote rehabilitation of bone damage
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骨髓巨噬细胞M2极化与脂肪干细胞成骨分化协同促进骨损伤康复
DOI：
10.1002/jcb.29297
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发表时间：
2019-07-24
影响因子：
4
通讯作者：
Yang, Pei
中科院分区：
文献类型：
--
作者：
Li, Yiyang;Kong, Ning;Yang, Pei
巨噬细胞通过分化成M1（促炎）和M2（抗炎）异质群体并调节两者之间的平衡，在健康和疾病的各种生理背景下，在宿主免疫反应中发挥关键作用。巨噬细胞除了调节先天和适应性免疫能力外，还决定性地参与组织稳态。然而，在组织损伤后，巨噬细胞是如何被调控的还远未阐明。在本研究中，我们发现脂肪源性干细胞（ADSCs）通过骨髓源性巨噬细胞（bmdm）向抗炎M2巨噬细胞的倾斜分化，明显促进体内骨缺损康复。体外数据表明，尽管在标准的组织培养分化条件下，ADSCs具有向成骨细胞和脂肪细胞分化的潜力，但这些间充质祖细胞在bmdms条件下主要受调节向成骨细胞分化，其转录因子2、骨保护素、骨甾体和核因子κ B配体受体激活因子下调。而与ADSCs共培养时，bmdm向M2巨噬细胞极化，具有较高水平的精氨酸酶1和甘露糖受体，但诱导型一氧化氮合酶和肿瘤坏死因子- α水平较低。总之，这些结果共同表明，ADSCs和宿主细胞通过相互调节分化和细胞因子分泌，协同促进骨修复。
By differentiating into and the balance being regulated between M1 (pro-inflammatory) and M2 (anti-inflammatory) heterogeneous populations, macrophages play critical roles during the host immune response in various physiological contexts in both health and diseases. Besides regulating innate and adaptive immune capacity, macrophages are also decisively involved in tissue homeostasis. However, how resident macrophages are regulated after tissue damages is still far from elucidation. In the present study, we found that adipose-derived stem cells (ADSCs) apparently promote bone defect rehabilitation in vivo via skewing differentiation of bone marrow-derived macrophage (BMDMs) towards anti-inflammatory M2 macrophages. In vitro data demonstrated that although ADSCs have the potential to differentiate to osteoblasts and adipose cells by using standard tissue culture-differentiating conditions, these mesenchymal progenitors are mainly regulated to differentiate into osteoblasts with overexpressed runt-related transcription factor 2, osteoprotegerin, osterix, and downregulated receptor activator of nuclear factor kappa B ligand in the presence of BMDMs-conditioned medium. Whereas BMDMs are polarized toward M2 macrophages with higher levels of arginase 1 and mannose receptor, but lower levels of inducible nitric oxide synthase and tumor necrosis factor-alpha when cocultured with ADSCs. In short, all these findings collectively demonstrated that ADSCs and resident host cells can synergistically contribute to the bony repair through mutual regulation of their differentiation and cytokine secretion.