Inhibiting role of long non-coding RNA LINC01197 in inflammation in rheumatoid arthritis through the microRNA-150/THBS2 axis.
长非编码 RNA LINC01197 通过 microRNA-150/THBS2 轴抑制类风湿关节炎炎症的作用。
- 作者列表："Zhao F","Dong J","Guo J","Bi L
PURPOSE:Rheumatoid arthritis (RA) is a commonly diagnosed systemic autoimmune disease. Aberrant expression of long non-coding RNAs (lncRNAs) is closely linked to the development of RA. This study was conducted to explore the functions of the lncRNA LINC01197 in RA progression. METHODS:Differentially expressed lncRNAs/microRNAs/mRNAs in patients with RA were analyzed using RNA microarrays. A mouse model with RA was established and RA-fibroblast-like synoviocytes (RA-FLS) were acquired for in vitro experiments. The function of LINC01197 in inflammation and RA progression in mice and its role in the viability of RA-FLS were determined by experiments involving its overexpression or suppression. The sub-cellular localization of LINC01197 was determined and the downstream molecules involved in LINC01197-mediated events were identified. RESULTS:LINC01197 was poorly expressed in the synovial tissues in the RA model mice. Overexpression of LINC01197 reduced RA severity in mice and inhibited proliferation and inflammatory responses as well as promoted apoptosis in RA-FLS. Online predictions and dual luciferase reporter gene assays suggested that LINC01197 could bind to miR-150 and further regulate THBS2 expression. LINC01197 promoted THBS2 expression through miR-150 sponging and inactivated the TLR4/NF-κB signaling pathway, thus alleviating RA inflammation. CONCLUSION:The current study suggested that LINC01197 sponged miR-150 to promote THBS2 expression, leading to TLR4/NF-κB inactivation, and ameliorated RA inflammation. These findings may offer new insights into RA treatment.
目的: 类风湿性关节炎 (RA) 是一种常见的系统性自身免疫性疾病。长链非编码 rna (lncRNAs) 的异常表达与 RA 的发生密切相关。本研究旨在探索 lncRNA LINC01197 在 RA 进展中的功能。 方法: 使用 RNA 微阵列分析 RA 患者中差异表达的 lncRNAs/microRNAs/mRNAs。建立 RA 小鼠模型，获得 RA 成纤维样滑膜细胞 (RA-FLS) 进行体外实验。通过涉及其过表达或抑制的实验确定 LINC01197 在小鼠炎症和 RA 进展中的功能及其在 RA-FLS 生存中的作用。确定了 LINC01197 的亚细胞定位，并确定了参与 LINC01197-mediated 事件的下游分子。 结果: LINC01197 在 RA 模型小鼠滑膜组织中呈低表达。过表达 LINC01197 可减轻小鼠 RA 的严重程度，抑制 RA-FLS 的增殖和炎症反应以及促进细胞凋亡。在线预测和双荧光素酶报告基因检测提示 LINC01197 可与 miR-150 结合，进一步调控 THBS2 的表达。LINC01197 通过 miR-150 海绵促进 THBS2 表达，灭活 TLR4/NF-κ b 信号通路，从而缓解 RA 炎症。 结论: LINC01197 海绵 miR-150 促进 THBS2 表达，导致 TLR4/NF-κ b 失活，改善 RA 炎症。这些发现可能为 RA 治疗提供新的见解。
METHODS:Purpose To determine outcomes of transphyseal ACL reconstruction using a living parental hamstring tendon allograft in a consecutive series of 100 children. Methods One hundred consecutive juveniles undergoing ACL reconstruction with a living parental hamstring allograft were recruited prospectively and reviewed 2 years after ACL reconstruction with IKDC Knee Ligament Evaluation, and KT1000 instrumented laxity testing. Skeletally immature participants obtained annual radiographs until skeletal maturity, and long leg alignment radiographs at 2 years. Radiographic Posterior tibial slope was recorded. Results Of 100 juveniles, the median age was 14 years (range 8–16) and 68% male. At surgery, 30 juveniles were graded Tanner 1 or 2, 21 were Tanner 3 and 49 were Tanner 4 or 5. There were no cases of iatrogenic physeal injury or leg length discrepancy on long leg radiographs at 2 years, despite a median increase in height of 8 cm. Twelve patients had an ACL graft rupture and 9 had a contralateral ACL injury. Of those without further ACL injury, 82% returned to competitive sports, IKDC ligament evaluation was normal in 52% and nearly normal in 48%. The median side to side difference on manual maximum testing with the KT1000 was 2 mm (range − 1 to 5). A radiographic PTS of 12° or more was observed in 49%. Conclusions ACL reconstruction in the juvenile with living parental hamstring tendon allograft is a viable procedure associated with excellent clinical stability, patient-reported outcomes and return to sport over 2 years. Further ACL injury to the reconstructed and the contralateral knee remains a significant risk, with identical prevalence observed between the reconstructed and contralateral ACL between 12 and 24 months after surgery. Level of evidence III (Cohort Study).
METHODS:Purpose The purpose of the study was to investigate the biomechanics of walking and of the knee joint in the acute phase of ACL injury. Methods We examined 18 patients with acute ACL injuries and 20 healthy adults as controls. The biomechanics of the knee joint and of walking was assessed by 5 inertial sensors fixed with special cuffs to the lower back, the lower third of the thigh, and the lower third of the shank of the right and left legs. The movements and temporal characteristics were recorded while the subject was walking 10 m at a comfortable pace. Based on the results of examination, the patients were divided into two groups: with severe function impairment (6 patients) and with moderate function impairment (12 patients). Results It was found that in the first days post-trauma, not only the knee function was reduced, but the function of the entire lower limb as well. This led to a functional asymmetry. The kinematics of movements in the joints changed in accordance with slower walking. The walking became not only slower, but it was also associated with a decreased impact load in the weight acceptance phase. At later dates, the functional impairments were less pronounced. The total range of flexion motion did not exceed 20 degrees in the first group and 55 degrees in the second one. The injured joint developed functional immobilization within the first days post-injury. This was a guarding response by additional muscle strain to prevent unusual and limit physiological movements in the knee joint. The movements in the knee joint while walking were of small amplitude, rocking, and occurred only under load. The amplitude of the main flexion in the swing phase was reduced. Conclusion The stage of an ACL injury should be assessed not only based on the time post-trauma, but also taking account of the functional parameter—the knee range of flexion while walking. According to our findings, the only factor that had influenced the functional condition of the KJ was the duration of joint immobilization after trauma.
METHODS:Purpose Numerous techniques have been described for the tibial-sided graft preparation in anterior cruciate ligament (ACL) reconstruction. The use of less suture material for graft preparation is thought to improve ingrowth and to reduce the risk for infection. At the same time, the suture construct should be strong enough to resist the surgeon’s pull during tensioning of the transplant. Methods In total, 39 fresh-frozen procine deep flexor tendons were used and prepared as four-strand grafts. In the three-suture group ( n = 19), graft preparation was performed using three tibial-sided sutures, with each tendon end sutured separately. In the one-suture group ( n = 20), a modified graft preparation using only one tibial-sided suture was applied. Each sample underwent load-to-failure testing ( N _max) after cyclic pre-loading. To estimate intraoperative tension forces acting on the tibial-sided suture constructs, the maximal tension force of 26 volunteers on such a construct was measured using a load cell. Results The biomechanical testing of the two different suture constructs showed a significantly higher load-to-failure for the three-suture group (711 N ± 91 N) compared to the one-suture group (347 N ± 24 N) ( p = 0.0001). In both groups, the mode of failure was a tear of the suture in all samples. A failure of the suture–tendon interface was not observed in any case. The median maximal tension force on the construct applied by the 26 volunteers was 134 N (range 73–182 N). Conclusion The presented single-suture tendon graft preparation resisted to smaller failure loads than the conventional three-suture technique. However, no failures in the suture–tendon interface were seen and the failure loads observed were far beyond the tension forces that can be expected intraoperatively. Hence, the single-suture graft preparation technique may be a valuable alternative to the conventional technique.