Insufficient attention has been focused on the directional migration of SOX10+ tendon stem cells (STSCs) during tendon remodeling. Here, we investigate whether tenascin-C (TNC) promotes STSC motility and migration. Based on the hypothesis that TNCs induce STSC migration, RNA-sequencing (RNA-seq) was conducted, identifying 2107 differentially expressed genes (DEGs), of which 1272 were up-regulated and 835 down-regulated following treatment with TNC versus the control. The DEGs were principally involved in cell adhesion and cell membrane signal transduction. Highly enriched-related signaling included the PI3K-Akt, focal adhesion, and ECM–receptor interaction pathways. Protein interaction analysis established that TNC was positively correlated with ITGA9 (integrin-α9). Furthermore, TNC activated the phosphorylation levels of FAK and Akt, and knockdown of ITGA9 with siRNA revealed that TNC contributes to STSC migration via the targeting of ITGA9. In addition, in vivo administration of TNC promoted tissue regeneration of injured tendons. In conclusion, TNC regulated the migration of STSCs via ITGA9, thereby promoting the regeneration of tendon injuries.

中文翻译：

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Tenascin-C 通过整合素-α9 调节 SOX10 肌腱干细胞的迁移以促进髌腱重塑

对肌腱重塑过程中 SOX10+ 肌腱干细胞 (STSCs) 的定向迁移的关注不足。在这里，我们调查了肌腱蛋白-C (TNC) 是否促进 STSC 运动和迁移。基于 TNC 诱导 STSC 迁移的假设，进行了 RNA 测序 (RNA-seq)，鉴定了 2107 个差异表达基因 (DEG)，其中 1272 个上调，835 个下调在 TNC 与对照处理后。DEGs主要参与细胞粘附和细胞膜信号转导。高度富集的相关信号包括 PI3K-Akt、粘着斑和 ECM-受体相互作用通路。蛋白质相互作用分析确定TNC与ITGA9（整合素-α9）呈正相关。此外，TNC 激活了 FAK 和 Akt 的磷酸化水平，和用 siRNA 敲低 ITGA9 表明 TNC 通过靶向 ITGA9 有助于 STSC 迁移。此外，体内施用 TNC 可促进受伤肌腱的组织再生。总之，TNC通过ITGA9调节STSCs的迁移，从而促进肌腱损伤的再生。