State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Center of Digital Dentistry, Faculty of Prosthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & NHC Key Laboratory of Digital Stomatology & Beijing Key Laboratory of Digital Stomatology & Key Laboratory of Digital Stomatology, Chinese Academy of Medical Sciences & NMPA Key Laboratory for Dental Materials, Beijing,100081, China.
Acta Biomater. 2024 Mar 1;176:432-444. doi: 10.1016/j.actbio.2024.01.001. Epub 2024 Jan 6.
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. STATEMENT OF SIGNIFICANCE: 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.
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在骨再生中至关重要。先前的研究主要集中在先天免疫细胞，如巨噬细胞上。现有的研究表明，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，调节 T 细胞募集和对于骨再生至关重要的特定亚群的机制尚不清楚。本研究表明，CD4 T 细胞对于双相磷酸钙（BCP）的异位成骨是必不可少的。随后，BCP 通过激活巨噬细胞中的钙通道来募集 CD4 T 细胞，从而释放趋化因子 Ccl3 和 Ccl17。最后，这些募集的 CD4 T 细胞主要是 Tregs，它们在 BCP 的异位成骨中起着重要作用。这些发现不仅阐明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。
骨替代材料的植入对于大骨缺损的愈合至关重要。现有的研究表明 T 淋巴细胞在骨再生中起着重要作用。然而，调节 T 细胞募集和对于骨再生至关重要的特定亚群的机制尚不清楚。在这项研究中，我们证明了双相磷酸钙（BCP）激活巨噬细胞中的钙通道导致它们释放趋化因子 Ccl3 和 Ccl17 来募集 CD4 T 细胞，主要是 Tregs，它们在 BCP 的异位成骨中起着关键作用。我们的发现为开发用于骨组织再生的骨替代材料提供了理论基础。
