SOX2 is crucial for the maintenance of the self-renewal capacity and multipotency of mesenchymal stem cells (MSCs); however, the mechanism by which SOX2 is regulated remains unclear. Here, we report that RNA interference of sirtuin 1 (SIRT1) in human bone marrow (BM)-derived MSCs leads to a decrease of SOX2 protein, resulting in the deterioration of the self-renewal and differentiation capacities of BM-MSCs. Using immunoprecipitation, we demonstrated direct binding between SIRT1 and SOX2 in HeLa cells overexpressing SOX2. We further discovered that the RNA interference of SIRT1 induces the acetylation, nuclear export, and ubiquitination of SOX2, leading to proteasomal degradation in BM-MSCs. SOX2 suppression by trichostatin A (TSA), a known histone deacetylase inhibitor, was reverted by treatment with resveratrol (0.1 and 1 mM), a known activator of SIRT1 in BM-MSCs. Furthermore, 0.1 and 1 mM resveratrol reduced TSA-mediated acetylation and ubiquitination of SOX2 in BM-MSCs. SIRT1 activation by resveratrol enhanced the colony-forming ability and differentiation potential to osteogenic and adipogenic lineages in a dose-dependent manner. However, the enhancement of self-renewal and multipotency by resveratrol was significantly decreased to basal levels by RNA interference of SOX2. These results strongly suggest that the SIRT1-SOX2 axis plays an important role in maintaining the self-renewal capability and multipotency of BM-MSCs. In conclusion, our findings provide evidence for positive SOX2 regulation by post-translational modification in BMMSCs through the inhibition of nuclear export and subsequent ubiquitination, and demonstrate that SIRT1-mediated deacetylation contributes to maintaining SOX2 protein in the nucleus.

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Background: Conflicting results have been reported concerning the progression of medial meniscal extrusion (MME) after arthroscopic transtibial pull-out repair of medial meniscus posterior root tear (MMRT), and no study has evaluated the relevant factors affecting the progression of MME. Purpose: To (1) evaluate the subjective and objective surgical outcomes of arthroscopic transtibial pull-out repair of MMRT and (2) identify relevant factors affecting the progression of MME after surgery. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 63 patients who underwent isolated arthroscopic transtibial pull-out repair of MMRT between January 2010 and June 2017 were evaluated retrospectively. Clinical scores and various radiographic parameters were evaluated to assess the surgical outcomes. The patients were classified into 2 groups according to the change in medial meniscal extrusion ratio (MMER) at 1 year after surgery compared with before surgery (group 1 consisted of 21 patients with reduced or maintained MMER; group 2 consisted of 42 patients with increased MMER). Variables including baseline demographics, radiographic parameters, and arthroscopic findings were compared to identify relevant factors affecting the progression of MME after surgery. Results: In the overall cohort, clinical outcomes at postoperative 2 years improved significantly ( P < .001 for visual analog scale score, International Knee Documentation Committee subjective score, and Lysholm score), whereas radiographic parameters showed an overall deterioration compared with the preoperative level. In subgroup comparisons, a significant difference was seen in the time from the onset of symptoms until surgery ( P < .001), defined as preoperative symptom duration, which a subsequent logistic regression analysis revealed to be a relevant factor associated with the progression of MMER ( P = .015). Both groups showed progression of radiographic osteoarthritis, but the progression was significantly higher in group 2 compared with group 1 at postoperative 2 years ( P = .032). On receiver operating characteristic curve analysis, the cutoff point for preoperative symptom duration associated with the progression of MMER was 13 weeks (sensitivity, 52.4%; specificity, 76.2%; accuracy, 72.4%). Conclusion: The arthroscopic transtibial pull-out repair of MMRT showed clinical improvement but did not prevent the progression of knee osteoarthritis, MME, or MMER. Although the preservation of MMER was not capable of completely preventing the progression of knee degeneration, MMER still has a potential clinical value in delaying the rate of progression of knee degeneration. Early surgical repair of MMRT, within 13 weeks from the onset of symptoms, might be helpful to prevent the progression of MME.

The objective of this paper was to evaluate in vivo material properties in order to address technical aspects of computational modeling of ligaments in the tibiofemoral joint using a probabilistic method. The laxity test was applied to the anterior-posterior drawer under 30° and 90° of flexion with a series of stress radiographs, a Telos device, and computed tomography. Ligament stiffness was investigated using sensitivity analysis based on the Monte-Carlo method with a subject-specific finite element model generated from in vivo computed tomography and magnetic resonance imaging data, subjected to laxity test conditions. The material properties of ligament stiffness and initial ligament strain in a subject-specific finite element model were optimized to minimize the differences between the movements of the tibia and femur in the finite element model and the computed tomography images in the laxity test. The posterior cruciate ligament was the most significant factor in flexion and posterior drawer, while the anterior cruciate ligament primarily was the most significant factor for the anterior drawer. The optimized material properties model predictions in simulation and the laxity test were more accurate than predictions based on the initial material properties in subject-specific computed tomography measurement. Thus, this study establishes a standard for future designs in allograft, xenograft, and artificial ligaments for anterior cruciate ligament and posterior cruciate ligament injuries.