Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling

Abstract

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti‐inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin‐treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO‐Ohpic and IGF‐1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down‐regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.

Bionic Silk Fibroin Film Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells by Activating Focal Adhesion Kinase

“…TSPCs were isolated and identified, as previously reported by the investigators [ 16 , 22 ]. Briefly, the Achilles tendon tissue was collected from three male 4-week-old Sprague Dawley (SD) rats (provided by the Animal Center of Third Military Medical University) after being euthanized.…”

MicroRNA engineered umbilical cord stem cell-derived exosomes direct tendon regeneration by mTOR signaling

“…Accordingly, the phosphorylation of AKT was significantly elevated after HUMSC-Exos treatment and act as the upstream inducing event for mTOR phosphorylation, whereas miR-29a antagonist produced the opposite results. In line with these results, PTEN/AKT signaling was also reported to be closely related to the TDSCs senescence and tendon atrophy [ 63 ], while decreasing PTEN/AKT signaling yielded benefits for inhibiting TDSCs adipogenesis and tendon fatty infiltration [ 64 ]. Thus, our results in this study collectively proposed that HUMSC-Exos might enhanced the tenogenic potential of TDSCs through modulating PTEN/AKT/mTOR pathway by transferring miR-29a.…”

Inhibition of PI3K/AKT/mTOR Signalling Pathway Activates Autophagy and Suppresses Peritoneal Fibrosis in the Process of Peritoneal Dialysis

“…Current studies have confirmed that EMT accompanied by high expression of PI3K, AKT and mTOR proteins occurs in PMCs under the stimulation of high-glucose dialysate (Deng et al, 2019). A study by Wang et al (2019) found that there is excessive activation of AKT in peritoneal EMT tissue, suggesting that the PI3K/AKT signalling pathway is involved in the EMT process of peritoneal tissue. After treatment with the PI3K/AKT pathway blocker wortmannin, the expression of p-AKT and α-SMA in PMCs was significantly inhibited (He et al, 2020).…”