<br>牙种植后巨噬细胞M1/M2极化动态适应微环境变化并调节牙槽骨重塑,Journal of Leukocyte Biology

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牙种植后巨噬细胞M1/M2极化动态适应微环境变化并调节牙槽骨重塑
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2021-07-12 , DOI: 10.1002/jlb.1ma0121-001r
Beilei Liang ₁ , Haicheng Wang ₂ , Di Wu ₁ , Zuolin Wang ₁

Affiliation

作为牙种植后最先到达的免疫细胞之一，Mφs 拥有极化为一系列不同表型的能力，从“经典激活”M1 Mφs 到“替代激活”M2 Mφs。在此，假设 Mphi 表型在牙种植后动态适应，并且这些变化随之而来的是与骨形成成骨细胞和骨吸收破骨细胞的协调相互作用的级联。结果显示，牙种植后的重塑过程与组织损伤的标准反应（以拔牙模型为例）相似，只是骨再生阶段延迟。此外，两组的Mφ激活都经历了从M1型Mφs主导到M2型主导阶段的转变，但M1型Mφs的持续存在发生在大鼠牙种植模型中。进一步的体外研究表明，M1 Mφs 通过分泌最高水平的 TNF-α 和 IL-1β 参与破骨细胞活动，并且是破骨细胞的潜在前体。此外，他们还通过分泌最高水平的化学引诱剂CCL2和VEGF来招募BMSC。 M2 Mphis 通过分泌成骨相关蛋白 BMP-2 和 TGF-β1 的能力，加速后续阶段的成骨。然而，当在高浓度条件培养基中培养时，各Mφ表型的BMSCs的成骨分化受到抑制，这意味着免疫策略应控制在适当的范围内。这些结果表明，M1 和 M2 Mφs 协调努力进行骨重塑，这可能突出了组织工程植入物的优化策略。

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Macrophage M1/M2 polarization dynamically adapts to changes in microenvironment and modulates alveolar bone remodeling after dental implantation

As one of the first arriving immune cells after dental implantation, Mϕs own the abilities to polarize into to a spectrum of diverse phenotypes, from “classically activated” M1 Mϕs to “alternatively activated” M2 Mϕs. Herein, it was hypothesized that Mϕ phenotypes dynamically adapt after dental implantation, and the changes ensue a cascade of coordinated interplay with the bone-forming osteoblast and the bone-resorbing osteoclast. Results showed that the remodelling process after dental implantation was similar with the standard response to tissue injury (exampled by tooth extraction models), only with the delay of bone regeneration phases. Additionally, Mϕ activation in both groups underwent a transition from M1 Mϕs dominated to M2-type dominated stage, but the persistence of M1 Mϕs occurred in rat model of dental implantation. Further research in vitro showed that M1 Mϕs are involved in osteoclast activities via secreting the highest levels of TNF-α and IL-1β, as well as being the potential precursor of osteoclasts. Besides, they also recruited BMSCs by secreting the highest levels of chemoattractants, CCL2 and VEGF. M2 Mϕs accelerated osteogenesis in the subsequent stage via their capability to secrete osteogenesis-related proteins, BMP-2 and TGF-β1. However, the osteogenic differentiation of BMSCs was inhibited when cultured in a high concentration of conditioned media from each Mϕ phenotype, meaning that the immune strategies should be controlled within the proper ranges. These results suggest that coordinated efforts by both M1 and M2 Mϕs for bone remodelling, which may highlight an optimization strategy for tissue engineering implants.

更新日期：2021-08-27

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