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Neglected immunoregulation: M2 polarization of macrophages triggered by low-dose irradiation plays an important role in bone regeneration |
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| Authors: | Shaoqing Chen Su Ni Chun Liu Mu He Yiwen Pan Pengfei Cui Cheng Wang Xinye Ni |
| Affiliation: | 1. The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China Jiangsu Province Engineering Research Center of Medical Physics, Changzhou, China Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Software (equal), Writing - original draft (equal);2. The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Software (equal), Supervision (equal);3. The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China Contribution: Data curation (equal), Methodology (equal), Software (equal);4. The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China Contribution: Data curation (equal), Investigation (equal), Software (equal);5. The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China School of Pharmacy, Changzhou University, Changzhou, China Contribution: Data curation (equal), Methodology (equal), Software (equal);6. School of Pharmacy, Changzhou University, Changzhou, China Contribution: Data curation (supporting), Software (equal);7. School of Pharmacy, Changzhou University, Changzhou, China Contribution: Data curation (supporting), Software (supporting);8. The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China |
| Abstract: | Current studies have found that low-dose irradiation (IR) can promote bone regeneration. However, mechanism studies of IR-triggered bone regeneration mainly focus on the effects of osteoblasts, neglecting the role of the surrounding immune microenvironment. Here in this study, in vitro proliferation experiments showed that low-dose IR ≤2 Gy could promote the proliferation of bone marrow mesenchymal stem cells (BMSCs), and qRT-PCR assay showed that low-dose IR ≤2 Gy could exert the M2 polarization of Raw264.7 cells, while IR >2 Gy inhibited BMSC proliferation and triggered M1 polarization in Raw264.7 cells. The ALP and mineralized nodules staining showed that low-dose IR ≤2 Gy not only promoted osteoblast mineralization through IR-triggered osteoblast proliferation but also through M2 polarization of Raw264.7 cells, while high-dose IR >2 Gy had the opposite effect. The co-incubation of BMSC with low-dose IR irradiated Raw264.7 cell supernatants increased the mRNA expression of BMP-2 and Osx. The rat cranial defects model revealed that low-dose IR ≤2 Gy gradually promoted bone regeneration, while high-dose IR >2 Gy inhibited bone regeneration. Detection of macrophage polarity in peripheral blood samples showed that low-dose IR ≤2 Gy increased the expression of CD206 and CD163, but decreased the expression of CD86 and CD80 in macrophages, which indicated M2 polarization of macrophages in vivo, while high-dose IR had the opposite effect. Our finding innovatively revealed that low-dose IR ≤2 Gy promotes bone regeneration not only by directly promoting the proliferation of osteoblasts but also by triggering M2 polarization of macrophages, which provided a new perspective for immune mechanism study in the treatment of bone defects with low-dose IR. |
| Keywords: | bone regeneration irradiation macrophage polarity osteoblast proliferation |