Previous studies have shown that the differentiation potential declines with the age of progenitor cells and is linked to altered levels of senescence markers. The purpose of this study was to test whether senescence marker p16 affects age-related tenogenic differentiation in tendon stem/progenitor cells (TSPCs). Young and aged TSPCs were isolated from young/healthy and aged/degenerated human Achilles tendons, respectively. Cellular aging and capacity for tenogenic differentiation were examined. The results showed that the tenogenic differentiation capacity of TSPCs significantly decreases with advancing age. TSPCs from elderly donors showed upregulation of senescence-associated β-galactosidase and p16 and concurrently a decrease in Type I collagen concentration and in the expressions of tendon-related markers: Scx, Tnmd, Bgn, Dcn, Col1, and Col3. Overexpression of p16 significantly inhibited tenogenic differentiation of young TSPCs. Analysis of the mechanism revealed that this effect is mediated by microRNA-217 and its target EGR1. These results indicated that p16 inhibits tenogenic differentiation of TSPCs via microRNA signaling pathways, which may serve as a potential target for the prevention or treatment in the future.

Tendon stem/progenitor cell (TSPC) senescence is often associated with age-dependent tendon diseases and greatly reduces the capacities for tendon repair and replacement. Exosomes contain bioactive molecules and have been increasingly used in regenerative medicine. In the present study, we demonstrated the anti-aging effects of young exosomes from circPVT1-overexpressing TSPCs at early passages (circPVT1-exo). These exosomes attenuated the phenotypes of aged TPSCs at late passages (L-TSPCs) by enhancing self-renewal and proliferation abilities and suppressing cell senescence, maintain their tenogenic capacity, and weaken their osteogenic differentiation. Mechanistically, circPVT1-exo inhibited the NF-κB pathway and increased SIRT1 expression in L-TSPCs. Knockdown of SIRT1 reversed these effects as evidenced by increased senescence, decreased proliferation, and tenogenic differentiation. These results suggest that circPVT1-exo may ameliorate aging-impaired TSPC function by modulating the SIRT1/NF-κB pathway, suggesting that circPVT1-exo has therapeutic potential for age-related diseases.

Background: Non-invasive diagnosis of distal tibiofibular syndesmosis instability (DTSI) was a great challenge to clinicians. We designed a new method, the Standing on single foot-Binding test, and investigated the accuracy of the test in the diagnosis of distal tibiofibular syndesmosis instability in adults with a history of ankle injury. Methods: 85 participants with ankle injury were subjected to the Standing on single foot-Binding test, MRI and palpation to detect the distal tibiofibular syndesmosis instability (DTSI) and the findings were compared with ankle arthroscopic results. Both participants and arthroscopist were blind to the predicted results of the clinical tests. Sensitivity, specificity, PPV, NPV, LR+, LR − and their 95% CIs were calculated for each of the clinical tests as well as for the positive clinical diagnosis. Results: The Standing on single foot-Binding test (SOSF-B test) outperformed MRI and palpation, in terms of sensitivity (87.5%/84.38%), specificity (86.79%/86.79%), PPV (80%/79.41%), NPV (92%/91.2%), LR+ (6.625/6.39), LR- (0.14/0.18) and diagnostic accuracy (87.06/85.88), among others, in the diagnosis of distal tibiofibular syndesmosis instability (DTSI). The diagnostic performance of 20° SOSF-B test was virtually identical to that of 0° SOSF-B test. According to the prevalence (28.7%) of DTSI and LR of four tests, the post-test probability could be used in clinical practice for the prediction of DTSI. Conclusion: This prospective and double-blind diagnostic test showed that the SOSF-B test is clinically feasible for the diagnosis of distal tibiofibular syndesmosis instability (DTSI), and new diagnostic tools for rapid screening of distal tibiofibular syndesmosis instability (DTSI). Level of evidence: II.