Clarification of the roles of SDF-1 on mesenchymal stem cells in bone graft healing-toward a clinical application for the improvement of allograft healing-

在原代rBMSCs向成骨细胞和软骨细胞分化过程中，SDF-1和CXCR4呈结构性表达。与同种异体移植模型相比，自体移植愈合后第2天SDF-1mRNA的表达增加了3.1倍。免疫组织化学分析显示，自体移植骨膜中有SDF-1蛋白的高表达。抗SDF-1抗体显著抑制了自体移植骨周围的新骨形成和MSCs的募集，而功能研究显示骨形成无明显增加。SDF-1以剂量依赖的方式上调rBMSCs的体外迁移，其作用可被CXCR4拮抗剂TN 14003抑制。这些结果表明，SDF-1在体内外对BMSCs均具有趋化作用，在正常骨修复的急性期起重要作用。然而，这些结果也表明SDF-1可能需要与其他分子合作才能实现成功的骨修复。

sDF-1 and CXCR4 were constitutively expressed by primary rBMSCs during osteoblastic and chondrocytic differentiation. The expression of SDF-1 mRNA was increased by 3.1 folds in the autograft healing at day 2 after surgery compared with that in the allograft model. Immunohistochemical analysis revealed the high expression of SDF-1 protein in the periosteum of the autografts. While the gain of function studies showed no remarkable increase in the bone formation, both the new bone formation around the autograft and the recruitment of MSCs were significantly inhibited by the administration of anti-SDF-1 antibody. SDF-1 upregulated the in vitro migration of rBMSCs in a dose dependent manner, and the effect was inhibited by TN 14003, an antagonist for CXCR4. These results indicate that SDF-1 has a chemotactic effect on BMSCs both in vitro and in vivo and plays a crucial role in the acute phase of normal bone repair. However, these results also suggest that SDF-1 may need to collaborate with other molecules to achieve a successful bone repair.