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. 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.