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.
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.
7 November 2017 in Journal of Orthopaedic Surgery and Research
The aim of this study was to compare the clinical outcome and postoperative complication between single-bundle anterior cruciate ligament (ACL) reconstruction with an anteromedial (AM) technique and a transtibial (TT) technique. The study includes clinical randomized controlled trials comparing the clinical outcomes of ACL reconstruction using the autologous hamstring tendon with an AM method and a TT method published up to September 2017 were retrieved from PubMed, Cochrane Library, and Embase databases. Relevant data were extracted and the Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality. Stata/SE 12.0 was used to perform a meta-analysis of the clinical outcome. Five RCTs were included, with a total of 479 patients: 239 patients and 240 patients in the AM group and the TT group, respectively. Assessing postoperative stability, better results were found in the AM group for the negative rate of the Lachman test (P < 0.05), the negative rate of the pivot-shift test (P < 0.05) and the side-to-side difference (P < 0.05). Assessing postoperative functional outcome, the AM group yielded superior results in proportion with International Knee Documentation Committee (IKDC) grade A (P < 0.05) and the Lysholm scores (P < 0.05) but had a comparable IKDC score (P > 0.05). In terms of postoperative complication, no significant difference was found between the AM group and the TT group (P > 0.05). The outcome of single-bundle ACL reconstruction with the AM technique is better than that with the TT technique in terms of postoperative stability and functional recovery of the knee.
The prior observational research on the impact of polyunsaturated fatty acid (PUFA) supplementation on osteoarthritis (OA) patients had yielded inclusive outcomes. This study utilized the Mendelian randomization (MR) approach to explore potential causal relationships between PUFAs and OA. The MR study was performed using GWAS summary statistics for PUFAs, encompassing omega-3 and omega-6 fatty acids, and for knee OA (KOA) and hip OA (HOA). The primary inverse-variance-weighted (IVW) method and two supplementary MR approaches were used to establish robust causality. Heterogeneity and horizontal pleiotropy were assessed using Cochrane’s Q and MR-Egger intercept tests. Additionally, a range of sensitivity analyses were conducted to strengthen the precision and reliability of the results. The IVW method indicated a potential genetic association between omega-3 fatty acids and KOA risk (odd ratio (OR) = 0.94, 95% confidence interval (CI): 0.89–1.00, p = 0.048). No significant correlation was found between omega-3 levels and HOA. Moreover, genetically predicted higher levels of omega-6 fatty acids were associated with a decreased risk of KOA (OR = 0. 93, 95% CI: 0.86–1.00, p = 0.041) and HOA (OR = 0.89, 95% CI: 0.82–0.96; p = 0.003). The MR-Egger intercept evaluation showed no horizontal pleiotropy affecting the MR analysis (all p > 0.05). Our findings supported the causal relationship between PUFAs and OA susceptibility and offered a novel insight that high omega-6 fatty acids may reduce the risk of KOA and HOA. These results underscore the importance of maintaining optimal levels of PUFAs, particularly omega-6 fatty acids, in individuals with a genetic predisposition to OA. Future research is necessary to validate these findings and elucidate the underlying mechanisms involved.
Hyperuricemia is a metabolic disorder that is essential to the development of inflammatory gout, with increasing prevalence over recent years. Emerging clinical findings has evidenced remarkable tendon damage in individuals with longstanding asymptomatic hyperuricemia, yet the impact of hyperuricemia on tendon homeostasis and associated repercussions is largely unknown. Here, we investigated whether asymptomatic hyperuricemia was associated with spontaneous ruptures in the Achilles tendon and the pathological effect of hyperuricemia on the tendon stem/progenitor cells (TSPCs). Significantly higher serum uric acid (SUA) levels were found in 648 closed Achilles tendon rupture (ATR) patients comparing to those in 12559 healthy volunteers. In vitro study demonstrated that uric acid (UA) dose dependently reduced rat Achilles TSPC viability, decreased the expressions of tendon collagens, and deformed their structural organization while significantly increased the transcript levels of matrix degradative enzymes and proinflammatory factors. Consistently, marked disruptions in Achilles tendon tissue structural and functional integrity were found in a rat model of hyperuricemia, together with enhanced immune cell infiltration. Transcriptome analysis revealed a significant elevation in genes involved in metabolic stress and tissue degeneration in TSPCs challenged by hyperuricemia. Specifically, reduced activity of the AKT-mTOR pathway with enhanced autophagic signaling was confirmed. Our findings indicate that asymptomatic hyperuricemia may be a predisposition of ATR by impeding the normal functions of TSPCs. This information may provide theoretical and experimental basis for exploring the early prevention and care of ATR.
19 October 2018 in Journal of Orthopaedic Surgery and Research
It is often technically demanding to find and remove loose bodies in several difficult locations like the popliteus hiatus and posterior compartment arthroscopically. We aim to present the technical aspects of establishing some special accessory portals to achieve arthroscopic removal of the loose bodies in these locations. From September 2010 to July 2017, 76 patients underwent removal of loose bodies in the popliteus hiatus and posterior compartment arthroscopically using some special accessory portal techniques. An auxiliary extreme lateral approach was established to remove loose bodies in the popliteus hiatus; a double-posteromedial portal was applied to handle loose body removal in the posteromedial compartment, and the posterior trans-septal portal was needed for loose body removal in the posterolateral compartment. Functional outcomes were evaluated using Lysholm score, Tegner score, and International Knee Documentation Committee (IKDC) score, respectively. Seventy-six patients (24 males and 52 females, average age 54.9 ± 11.4) finished the follow-up visit at 3 weeks after surgery. There was no statistically significant difference among the three groups in demographics. All the patients were performed following the special technique. According to a comparison of knee joint scores before and after surgery, all the patients obtained good prognosis using some special accessory portals in loose body removal. With the help of the above accessory portals under endoscopic visualization, loose bodies in the popliteus hiatus and posterior compartment of the knee can be safely and effectively removed.