Interleukin-34 as a promising clinical biomarker and therapeutic target for inflammatory arthritis

Interleukin-34 (IL-34), recently identified as a novel inflammatory cytokine and the second ligand for colony-stimulating factor-1 receptor, is known to play regulatory roles in the development, maintenance, and function of mononuclear phagocyte lineage cells – especially osteoclasts. Regarding its primary effect on osteoclasts, IL-34 has been shown to stimulate formation and activation of osteoclasts, which in turn magnifies osteoclasts-resorbing activity. In addition to its role in osteoclastogenesis, IL-34 has been implicated in inflammation of synovium via augmenting production of inflammatory mediators, in which altered IL-34 expression is regulated by pro-inflammatory cytokines responsible for cartilage degradation. Indeed, IL-34 has been documented to be highly expressed in inflamed synovium of rheumatoid arthritis (RA) and knee osteoarthritis (OA) patients, which are recognized as inflammatory arthritis. Furthermore, a number of clinical studies demonstrated that IL-34 levels were significantly increased in the circulation and synovial fluid of patients with RA and knee OA. Its levels were also found to be positively associated with disease severity – especially radiographic severity of both RA and knee OA patients. Interestingly, emerging evidence has accumulated that functional blockage of IL-34 with specific antibody can alleviate the severity of inflammatory arthritis. It is therefore reasonable to speculate that IL-34 may be developed as a potential biomarker and a new therapeutic candidate for inflammatory arthritis. To date, there are numerous studies showing IL-34 involvement and association with many aspects of inflammatory arthritis. Herein, this review aimed to summarize the recent findings regarding regulatory role of IL-34 in synovial inflammation-mediated cartilage destruction and update the current comprehensive knowledge on usefulness of IL-34-based treatment in inflammatory arthritis – particularly RA and knee OA.     

新辅助化疗联合人工膝关节置换治疗膝关节附近骨肉瘤

目的:评价新辅助化疗联合人工膝关节置换治疗膝关节附近骨肉瘤的临床疗效。方法:38例膝关节附近骨肉瘤采用新辅助化疗和人工膝关节置换,所有病例均进行肿瘤细胞坏死率、5年内肿瘤局部复发率、5年生存率和膝关节功能评估。结果:38例患者新辅助化疗后肿瘤细胞坏死率平均95.8%;随访6-9年,38例患者中5年内肿瘤局部复发12例(31.6%),5年后生存31例(81.6%),膝关节功能优良率92.1%。结论:新辅助化疗联合人工膝关节置换治疗膝关节附近骨肉瘤可有效提高骨肉瘤5年生存率,保存患肢功能,是骨肉瘤保肢治疗的一种较好的方法。     

24例人工全膝关节置换术患者手术前后的护理

目的：观察2000年3月至2003年4月人工全膝关节置换术（TKR）患者围手术期进行系统康复训练的护理.方法：选择接受TKR的患者24例30个膝关节,入院后进行术前康复教育和肢体的康复训练（包括肌肉、关节训练及步态训练等）,术后护理包括有针对性的心理护理及系统规范的康复训练.结果：本组术后随访6-12周,效果满意,优良率达95.8%,未发生并发症.结论：TKP患者围手术期间进行系统康复训练,可以减少膝关节并发症,增强膝关节活动范围,满足日常生活所需的关节活动,提高生活质量.     

利用寡核苷酸芯片分析Smad3基因敲除小鼠关节软骨细胞基因表达谱的改变

此前发现 Smad3 基因敲除小鼠(Smad3ex8/ex8)的关节软骨细胞异常肥大分化,出现类似于人类骨关节炎的表型。为了进一步明确转化生长因子-β(TGF-β)/Smad3 信号通过调节哪些靶基因的表达来抑制关节软骨细胞的肥大分化,以及研究骨关节炎发病的分子机制,利用寡核苷酸芯片技术分析了 5 日龄 Smad3 基因敲除小鼠与野生型对照小鼠关节软骨细胞基因表达谱的改变。通过对差异表达基因的分析,发现在 Smad3 基因敲除小鼠软骨细胞中骨形态发生蛋白(BMP)与 TGF-β/细胞分裂周期基因 42(Cdc42)信号通路活性增强。此外,还发现其他信号通路,如生长激素(growth hormone)/胰岛素样生长因子 1(Igf1)以及成纤维细胞生长因子(Fgf)信号通路相关基因表达的改变。值得注意的是,还发现了 Smad3 基因敲除小鼠软骨细胞中蛋白合成与电子传递链相关基因的表达水平普遍上调,这意味着蛋白质合成速率的加快与细胞有氧呼吸的增强可能与关节软骨细胞的肥大分化和骨关节炎的发生相关。     

电针足少阳经穴联合本体感觉训练对膝关节骨性关节炎患者步行能力、血液流变学和骨代谢的影响

摘要 目的：探讨电针足少阳经穴联合本体感觉训练对膝关节骨性关节炎（KOA）患者步行能力、血液流变学和骨代谢的影响。方法：按照随机数字表法,将2019年8月~2022年1月期间于我院就诊的KOA患者204例分为对照组（102例,本体感觉训练）和研究组（102例,电针足少阳经穴联合本体感觉训练）。对比两组膝关节功能、疼痛症状、步行能力、血液流变学和骨代谢情况。结果：治疗4周后,两组视觉疼痛模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎调查量表（WOMAC）评分下降,Lysholm 膝关节功能评分升高,且研究组的改变程度大于对照组（P<0.05）。治疗4周后,两组双支撑相下降,步速、步长升高,且研究组的改变程度大于对照组（P<0.05）。治疗4周后,两组纤维蛋白原、红细胞聚集指数、全血黏度（高切）、全血黏度（低切）下降,研究组的改变程度大于对照组（P<0.05）。治疗4周后,两组碱性磷酸酶（ALP）、骨钙素（BGP）、骨特异性碱性磷酸酶（BALP）水平升高,研究组的改变程度大于对照组（P<0.05）。结论：电针足少阳经穴联合本体感觉训练可改善KOA患者的疼痛症状,促进膝关节功能恢复,改善步行能力,作用机制可能与调节血液流变学和骨代谢有关。     

Cdkn2a示踪小鼠:研究创伤性骨关节炎软骨退变细胞衰老的新模型

骨关节炎(osteoarthritis,OA)是临床上最为常见的老年性运动系统疾病之一。研究表明,衰老是OA发生发展的重要影响因素之一,但其具体作用及机制尚未完全清楚。本研究通过CRISPR/Cas9技术,建立了Cdkn2a-e(Luc-2A-tdTomato-2A-CreERT2-WPRE-pA)1定点敲入的杂合子小鼠模型,可在小鼠活体内追踪衰老经典标记物Cdkn2a(p16, p16INK4a)的表达情况,结合前交叉韧带横断术(ACLT)诱导OA小鼠模型,将OA病理进程中的衰老变化在体外直观呈现,明确衰老与OA之间的关系。本研究选取10 ～ 12周龄Cdkn2a小鼠,随机分为非手术对照组、假手术组和ACLT组,通过ACLT手术在小鼠中构建OA的模型,术后4周收取动物进行活体荧光成像检测显示,ACLT组术后4周的小鼠膝关节局部Cdkn2a荧光表达升高(P＜0.05),小鼠膝关节组织切片的番红O固绿染色显示,4周时ACLT组膝关节软骨出现退变(P＜0.05),对小鼠膝关节组织进行Cdkn2a免疫组织化学染色,相较其他2个组,ACLT组的小鼠膝关节组织软骨表面Cdkn2a染色更深。研究结果显示,通过手术诱导的OA模型在局部具有衰老的表现,这进一步验证了衰老和OA的关系。同时,该Cdkn2a示踪小鼠模型能够在活体小鼠内体现衰老的进展。结合影像学检查,可以实时观察衰老和OA发生、进展的关系,为衰老与OA疾病机制的研究提供了良好的模型,也为今后进行靶向衰老进行OA的治疗提供了很好的研究工具。     

小分子药物BNTA通过上调Insig1缓解高胆固醇引起的骨关节炎

骨关节炎(osteoarthritis,OA)是运动系统常见的退行性疾病,具有高发病率和高致残率。骨关节炎的发病机制目前尚不明确,既往研究认为骨关节炎发病主要与创伤因素相关,而近期研究表明,以胆固醇代谢异常为主的代谢性因素同样与骨关节炎密切相关,骨关节炎的治疗以早期对症治疗和晚期手术治疗为主,尚无针对病因的特效药物。既往研究中发现,有一种具有软骨保护作用的小分子药物BNTA,其在创伤引起的骨关节炎中具有较好的疗效,但其对高胆固醇引起的骨关节炎的作用尚不明确。本研究为探究BNTA对高胆固醇引起的骨关节炎的治疗作用及其机制,采用高胆固醇饮食构建了大鼠骨关节炎模型,取膝关节石蜡切片进行组织学评估,使用油红O染色评估大鼠软骨细胞内的脂质积聚情况,使用RT-qPCR、免疫荧光和免疫组化评估软骨细胞合成代谢、分解代谢及胆固醇代谢相关基因和蛋白质的表达。结果显示,BNTA可缓解高胆固醇大鼠骨关节炎模型中的病理表现,改善OARSI评分。在大鼠软骨细胞中,BNTA可促进合成代谢相关基因col2、sox9、acan的表达,抑制分解代谢相关基因mmp13、adamts5的表达,可改善高胆固醇引起的大鼠软骨细胞脂质积聚。在大鼠软骨细胞和高胆固醇大鼠骨关节炎模型中BNTA均可上调Insig1表达。本研究证实,高胆固醇可在体内和体外实验中加重骨关节炎,可引起大鼠软骨细胞脂质积聚增加。在体内和体外实验中BNTA均能缓解高胆固醇引起的骨关节炎表型,改善软骨细胞内的异常脂质积聚,其作用可能为通过上调Insig1抑制细胞内的胆固醇生物合成,从而缓解脂质异常积聚。     

Neuromuscular activation of quadriceps bellies during tasks performed in the same biomechanical condition in patients undergoing total knee arthroplasty

ObjectiveTo investigate neuromuscular activation of quadriceps bellies during different tasks in patients before and after total knee arthroplasty (TKA).MethodsTwenty-six patients scheduled for TKA and 16 control subjects performed three isometric tasks: knee extension (KE), hip flexion (HF), hip flexion with contralateral hip extension (HFE). Surface electromyography signals of rectus femoris, vastus medialis and vastus lateralis were collected the day before (T0), at one (T1) and three (T2) days after surgery, whereas control subjects underwent a single evaluation. The Root Mean Square peak normalized for its highest value during the three tasks (nRMS-peak) was used as index of maximum neuromuscular activation for each belly. Sixteen patients performed the postoperative assessment, due to the placement of an elastomeric pump aimed at reducing pain in 10 patients.ResultsPatients showed lower rectus femoris nRMS-peak during KE compared to HF and HFE before and after surgery (p < 0.001), as occurred in control subjects. Differently from control subjects, patients showed higher vastus medialis and vastus lateralis nRMS-peak during HF compared to KE at T1 (p = 0.008) and T2 (p = 0.039).ConclusionTKA modified quadriceps neuromuscular activation during different tasks performed the same biomechanical condition. These findings may be considered in planning physiotherapy interventions after TKA.     

The choice of the femoral center of rotation affects material loss in total knee replacement wear testing – A parametric finite element study of ISO 14243-3

A leading cause of long-term failure of total knee replacements (TKRs) is osteolysis caused by polyethylene wear particles. The current gold standard for preclinical wear testing of TKRs is mechanical knee simulators. The definition of the femoral center of flexion-extension rotation (CoR) has been identified as one possible source of variability within TKR wear tests, since the femoral curvature varies from distal to posterior. The magnitude of the influence on wear due to changes in location of femoral CoR has not been investigated in depth. During this study, a computational framework utilizing finite element analysis for modelling wear of TKRs was developed and used to investigate the influence of the location of femoral CoR on TKR polyethylene wear during standardized displacement controlled testing (ISO 14243-3:2014). The study was carried out using a 40-point Latin Hypercube Design of Experiments approach. Volumetric wear was highly correlated to femoral CoR in both the superior/inferior and anterior/posterior directions, with a stronger relationship in the superior/inferior direction. In addition, wear scars showing linear penetration were examined, with large differences in simulations at the extreme ends of the sampling region. In this study, it was found that variations in the location of the femoral center of rotation can represent a large source of variability in the preclinical testing and evaluation of the wear performance of total knee replacements. This study represents the first attempt at quantifying the effect on wear of different femoral center of rotations across a large sampling space.