Background: Recent studies have shown that bone marrow stromal cell-derived exosomes (BMSC-Exos) can be used for tissue repair. However, whether the BMSC-Exos can promote tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is still unclear. In this study, we observed in vivo and in vitro the effect of rat BMSC-Exos on tendon-bone healing after ACLR and its possible mechanism. Methods: Highly expressed miRNAs in rat BMSC-Exos were selected by bioinformatics and verified in vitro. The effect of overexpressed miRNA in BMSC-Exos on M2 macrophage polarization was observed. A rat model of ACLR was established. The experimental components were divided into three groups: the control group, the BMSC-Exos group, and the BMSC-Exos with miR-23a-3p overexpression (BMSC-Exos mimic) group. Biomechanical tests, micro-CT, and histological staining were performed for analysis. Results: Bioinformatics analysis showed that miR-23a-3p was highly expressed in rat BMSC-Exos and could target interferon regulatory factor 1 (IRF1, a crucial regulator in M1 macrophage polarization). In vitro, compared with the control group or the BMSC-Exos group, the BMSC-Exos mimic more significantly promoted the polarization of macrophages from M1 to M2. In vivo, at 2 weeks, the number of M2 macrophages in the early local stage of ACLR was significantly increased in the BMSC-Exos mimic group; at 4 and 8 weeks, compared with the control group or the BMSC-Exos group, the bone tunnels of the tibia and femur sides of the rats in the BMSC-Exos mimic group were significantly smaller, the interface between the graft and the bone was narrowed, the bone volume/total volume ratio (BV/TV) increased, the collagen type II alpha 1 level increased, and the mechanical strength increased. Conclusions: BMSC-Exos promoted M1 macrophage to M2 macrophage polarization via miR-23a-3p, reduced the early inflammatory reaction at the tendon-bone interface, and promoted early healing after ACLR.
3 November 2012 in Knee Surgery, Sports Traumatology, Arthroscopy
Osteoarthritis (OA) is significantly associated with diabetes, but how hyperglycemia induces or aggravates OA has not been shown. The synovium plays a critical role in cartilage metabolism and substance exchange. Herein, we intended to investigate whether and how hyperglycemia affects the occurrence and progression of OA by influencing the synovium. In patients with knee OA and diabetes (DM OA), we found a more severe inflammatory response, higher endoplasmic reticulum stress (ERS) levels, and more advanced glycosylation end products (AGEs) accumulation in the synovium than in patients without diabetes. Subsequently, we found similar results in the DM OA group in a rat model. In the in vitro cocultivation system, high glucose-stimulated AGEs accumulation, ERS, and inflammation in rat fibroblast-like synoviocytes (FLSs), which resulted in chondrocyte degeneration due to inflammatory factors from FLSs. Furthermore, in the synovium of the DM OA group and FLSs treated with high glucose, the expression of glucose transporter 1 (GLUT1) and its regulatory factor hypoxia-inducible factor (HIF)-1α was increased significantly. Inhibitors of HIF-1α, GLUT1 or AGEs receptors attenuated the effect of high glucose on chondrocyte degradation in the FLS-chondrocyte coculture system. In summary, we demonstrated that hyperglycemia caused AGEs accumulation in FLSs via the HIF-1α-GLUT1 pathway, which increases the release of inflammatory factors from FLSs, subsequently inducing chondrocyte degradation and promoting OA progression.
10 March 2018 in Journal of Orthopaedic Surgery and Research
Both single-bundle (SB) and double-bundle (DB) techniques were widely used in anterior cruciate ligament (ACL) reconstruction recently. Nevertheless, up to now, no consensus has been reached on whether the DB technique was superior to the SB technique. Moreover, follow-up of the included studies in the published meta-analyses is mostly short term. Our study aims to compare the mid- to long-term outcome of SB and DB ACL reconstruction concerning knee stability, clinical function, graft failure rate, and osteoarthritis (OA) changes. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Embase, and the Cochrane Library were searched from inception to October 2017. The study included only a randomized controlled trial (RCT) that compared SB and DB ACL reconstruction and that had a minimum of 5-year follow-up. The Cochrane Collaboration’s risk of bias tool was used to assess the risk of bias for all included studies. Stata/SE 12.0 was used to perform a meta-analysis of the clinical outcome. Five RCTs were included, with a total of 294 patients: 150 patients and 144 patients in the DB group and the SB group, respectively. Assessing knee stability, there was no statistical difference in side-to-side difference and negative rate of the pivot-shift test. Considering functional outcome, no significant difference was found in proportion with International Knee Documentation Committee (IKDC) grade A, IKDC score, Lysholm scores, and Tegner scores. As for graft failure rate and OA changes, no significant difference was found between the DB group and the SB group. The DB technique was not superior to the SB technique in autologous ACL reconstruction regarding knee stability, clinical function, graft failure rate, and OA changes with a mid- to long-term follow-up.
6 December 2013 in Journal of International Medical Research
Objective: To determine interleukin (IL)-17 concentrations in serum and synovial fluid from patients with knee osteoarthritis, and evaluate their correlation with disease severity. Methods: Serum and synovial fluid were collected from patients with primary knee osteoarthritis; age- and sex-matched healthy control subjects provided serum samples. This study was conducted retrospectively. IL-17 was quantified by enzyme-linked immunosorbent assay. Osteoarthritis severity and grade were assessed using the Lequesne index and Kellgren and Lawrence (KL) grading system, respectively. Results: Serum IL-17 concentrations were significantly higher in patients ( n = 98) than in controls ( n = 50). In the patient group, the synovial fluid IL-17 concentration increased significantly with KL grade and was significantly positively correlated with Lequesne index ( r = 0.6232). Conclusions: The synovial fluid IL-17 concentration could represent a useful biochemical marker to reflect knee osteoarthritis severity and progression.