A ligature-induced periodontitis model was established in wild-type and CD146CreERT2; RosatdTomato mice to explore the function of pericytes in alveolar bone formation. We found that during periodontitis progression and periodontal wound healing, CD146+/NG2+ pericytes were enriched in the periodontal tissue areas, which could migrate to the alveolar bone surface and colocalize with ALP+/OCN+ osteoblasts. Chemokine C-X-C motif receptor 4 (CXCR4) inhibition using AMD3100 blocked CD146-Cre+ pericyte migration and osteogenesis, as well as further exacerbated periodontitis-associated bone loss. Next, primary pericytes were sorted out by magnetic-activated cell sorting and demonstrated that C-X-C motif chemokine ligand 12 (CXCL12) promotes pericyte migration and osteogenesis via CXCL12-CXCR4-Rac1 signaling. Finally, the local administration of an adeno-associated virus for Rac1 overexpression in NG2+ pericytes promotes osteoblast differentiation of pericytes and increases alveolar bone volume in periodontitis. Thus, our results provided the evidence that pericytes may migrate and osteogenesis via the CXCL12-CXCR4-Rac1 axis during the pathological process of periodontitis.

中文翻译：

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周细胞迁移和成骨在牙周炎中的作用


在野生型和CD146CreERT2中建立结扎诱导的牙周炎模型； RosatdTomato 小鼠探索周细胞在牙槽骨形成中的功能。我们发现，在牙周炎进展和牙周伤口愈合过程中，CD146+/NG2+周细胞在牙周组织区域富集，可以迁移到牙槽骨表面并与ALP+/OCN+成骨细胞共定位。使用 AMD3100 抑制趋化因子 CXC 基序受体 4 (CXCR4) 可阻断 CD146-Cre+ 周细胞迁移和成骨，并进一步加剧牙周炎相关的骨质流失。接下来，通过磁激活细胞分选来分选初级周细胞，并证明 CXC 基序趋化因子配体 12 (CXCL12) 通过 CXCL12-CXCR4-Rac1 信号传导促进周细胞迁移和成骨。最后，局部给予NG2+周细胞中Rac1过表达的腺相关病毒可促进周细胞的成骨细胞分化并增加牙周炎中的牙槽骨体积。因此，我们的研究结果证明，在牙周炎的病理过程中，周细胞可能通过CXCL12-CXCR4-Rac1轴迁移和成骨。