PI3K-Akt signaling regulates Scx-lineage tenocytes and Tppp3-lineage tendon sheath synovial cells in physiological tendon regeneration

We identify a PI3K-Akt signaling pathway which is specifically upregulated in neonatal murine injured Achilles tendons. PI3K-Akt signaling inhibition in neonatal murine Achilles tendon rupture model decreases cell proliferation and cell migration to the regenerating tendons in both Scx-lineage intrinsic tenocytes and Tppp3-lineage extrinsic tendon sheath synovial cells. Moreover, PI3K-Akt signaling inhibition decreases stemness and promotes mature tenogenic differentiation in both Scx-lineage and Tppp3-lineage cells. Collectively, PI3K-Akt signaling plays an important role in physiological tendon regeneration. Overall design: mRNA was extracted from uninjured Achilles tendons and injured Achilles tendons in 7-day old and 6-months-old mice. mRNA profiles were analyzed by deep sequencing using Illumina Miseq.

我们鉴定出一条在新生小鼠受损跟腱中特异性上调的PI3K-Akt信号通路（PI3K-Akt signaling pathway）。在新生小鼠跟腱断裂模型中抑制该通路，可同时降低Scx谱系固有肌腱细胞与Tppp3谱系外源性腱鞘滑膜细胞向再生肌腱的增殖与迁移能力。此外，抑制PI3K-Akt信号通路还可降低上述两类细胞的干细胞干性，并促进其向成熟肌腱细胞的分化。综上，PI3K-Akt信号通路在生理性肌腱再生过程中发挥重要作用。
实验设计：从7日龄及6月龄小鼠的未受损跟腱与受损跟腱中提取mRNA，采用Illumina Miseq平台进行深度测序以分析mRNA表达谱。