<br>双相磷酸钙招募 Tregs 促进骨再生,Acta Biomaterialia

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双相磷酸钙招募 Tregs 促进骨再生
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2024-01-06 , DOI: 10.1016/j.actbio.2024.01.001
Jiaojiao Li ₁ , Ting Xia ₁ , Qin Zhao ₁ , Can Wang ₁ , Liangliang Fu ₁ , Zifan Zhao ₂ , Ziqiao Tang ₁ , Chenghu Yin ₁ , Min Wang ₁ , Haibin Xia ₁

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骨替代材料的使用对于大骨缺损的愈合至关重要。骨替代材料诱导的免疫反应对于骨再生至关重要。先前的研究主要集中在先天免疫细胞，例如巨噬细胞。现有研究表明，T淋巴细胞作为适应性免疫细胞，在骨再生中发挥着不可或缺的作用。然而，控制 T 细胞募集和骨再生所必需的特定亚群的机制仍不清楚。这项研究表明，CD4 T 细胞对于双相磷酸钙 (BCP) 异位成骨是不可或缺的。随后，CD4 T 细胞的募集与 BCP 激活巨噬细胞中的钙通道释放趋化因子 Ccl3 和 Ccl17 密切相关。最后，这些招募的 CD4 T 细胞主要是 Tregs，它们在 BCP 异位成骨中发挥重要作用。这些发现不仅揭示了骨替代材料植入后的免疫再生过程，而且为开发促进骨组织再生的骨替代材料奠定了理论基础。骨替代材料植入对于大骨缺损的愈合至关重要。现有研究表明 T 淋巴细胞有助于骨再生。然而，控制 T 细胞募集的具体机制以及骨再生所必需的特定亚群仍不清楚。在这项研究中，我们证明双相磷酸钙 (BCP) 激活巨噬细胞中的钙通道会导致巨噬细胞释放趋化因子 Ccl3 和 Ccl17，以招募 CD4 T 细胞（主要是 Tregs），这些细胞在 BCP 的异位成骨中发挥着至关重要的作用。我们的研究结果为开发用于骨组织再生的骨替代材料提供了理论基础。

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Biphasic calcium phosphate recruits Tregs to promote bone regeneration

The use of bone substitute materials is crucial for the healing of large bone defects. Immune response induced by bone substitute materials is essential in bone regeneration. Prior research has mainly concentrated on innate immune cells, such as macrophages. Existing research suggests that T lymphocytes, as adaptive immune cells, play an indispensable role in bone regeneration. However, the mechanisms governing T cell recruitment and specific subsets that are essential for bone regeneration remain unclear. This study demonstrates that CD4 T cells are indispensable for ectopic osteogenesis by biphasic calcium phosphate (BCP). Subsequently, the recruitment of CD4 T cells is closely associated with the activation of calcium channels in macrophages by BCP to release chemokines Ccl3 and Ccl17. Finally, these recruited CD4 T cells are predominantly Tregs, which play a significant role in ectopic osteogenesis by BCP. These findings not only shed light on the immune-regenerative process after bone substitute material implantation but also establish a theoretical basis for developing bone substitute materials for promoting bone tissue regeneration. Bone substitute material implantation is essential in the healing of large bone defects. Existing research suggests that T lymphocytes are instrumental in bone regeneration. However, the specific mechanisms governing T cell recruitment and specific subsets that are essential for bone regeneration remain unclear. In this study, we demonstrate that activation of calcium channels in macrophages by biphasic calcium phosphate (BCP) causes them to release the chemokines Ccl3 and Ccl17 to recruit CD4 T cells, predominantly Tregs, which play a crucial role in ectopic osteogenesis by BCP. Our findings provide a theoretical foundation for developing bone substitute material for bone tissue regeneration.

更新日期：2024-01-06

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