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.
Highlights
Tendons are anatomical structures connecting muscles to bone which generate transmission of forces, thereby ensuring joint movements
How to inhibit and reverse the fatty infiltration is an important issue for injury tendon healing process
A representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), have been widely used in clinical for their pain relief and anti‐inflammation effect through inhibiting the function of cyclooxygenase enzymes and prostaglandins,[20] and Tendon stem cells (TSCs) play an irreplaceable role in repair process of tendinopathy, but the effect of aspirin on adipogenic differentiation of TSCs and fatty infiltration is still unclear
Summary
Tendons are anatomical structures connecting muscles to bone which generate transmission of forces, thereby ensuring joint movements. To inhibit TSCs adipogenic differentiation is vital to regain tendon structure and function. NSAIDs have been widely used in clinical practice for their anti‐ inflammation and relieving pain through inhibiting prostaglandin. As the classic representative of NSAIDs, has been used in many clinical fields, such as cardiovascular system,[9] central nervous system,[10] some cancers[11] and tendinopathy/tendon injury. Its anti‐ inflammation and pain relief effect have been widely accepted, but evidence of its effect on TSCs differentiation is lacking, especially its effect on adipogenic differentiation and injury tendon healing. The present study aimed to investigate the effect of aspirin on TSCs adipogenic differentiation and fatty infiltration in injury tendon, find out the molecular difference and related signalling through RNA sequencing and provide new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy
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