大鼠膝骨关节炎滑膜细胞原代培养

目的:建立原代培养膝骨关节炎大鼠滑膜细胞的方法。方法:取膝骨关节炎大鼠膝关节滑膜组织,用酶消化法消化、分离细胞,用DMEM培养液进行培养并传代,观察滑膜细胞生长状况、并用细胞形态学及细胞免疫化学鉴定。结果:用酶消化法培养膝骨关节炎滑膜细胞,方法简单、成功率高、细胞形态典型。结论:单一的胶原酶消化法是一种有效的滑膜细胞原代培养的方法,可以满足一般实验需求。     

探讨肠道菌群对膝骨关节炎治疗的影响

膝骨关节炎是一种中老年人常见的慢性疾病,因其发病率及致残率高,严重影响患者的生存质量。膝骨关节炎不仅增加了患者及其家庭乃至社会的经济压力,而且还加重了心理负担。治疗方案虽然多,但目前尚无根治方法,而且疗效也参差不齐。肠道菌群作为人体巨大的微生物宝库,拥有着很大的潜力,这使之成为了科研领域一个新的研究热点,其对膝骨关节炎的影响也成为了人们关注的焦点。本文通过查阅相关文献,从慢性炎症、代谢性疾病、成骨细胞以及破骨细胞这四个方面来阐述和总结肠道菌群与膝骨关节炎的关系,以期为临床上治疗膝骨关节炎提供新的方法与思路。     

降钙素治疗膝骨关节炎的疗效观察

目的:观察和评价应用密盖息治疗膝骨关节炎的疗效.方法:40例女性病人,年龄50-75岁,平均年龄65岁,均经过临床X线检查确诊,应用密盖息四周后,对疼痛缓解时间、功能恢复情况进行疗效评估,并经一年门诊随访,总结其疗效.结果:随访1年后,统计达到优20例,良17例,无效3例,总有效率80%以上.结论:密盖息对膝骨关节炎治疗达到止痛、控制和预防膝骨关节内翻、外翻畸形,在临床治疗提高疗效起到巨大的作用.     

右归丸对鼠膝骨性关节炎的治疗作用及Wnt信号通路相关因子表达的影响

目的：分析右归丸对膝骨性关节炎（KOA）大鼠Wnt信号通路相关因子表达的影响,探讨右归丸对KOA大鼠的保护机制。方法：SPF级SD大鼠60只,按照体重法随机分为假手术组、模型组、硫酸氨基葡萄糖组、右归丸高、中、低剂量组（n=10）。采用改良Hulth法复制膝骨关节炎大鼠模型。右归丸高中低剂量组分别按20、10、5 g/kg灌服相应的药物,硫酸氨基葡萄糖组按0.17 g/kg灌服硫酸氨基葡萄糖,假手术组和模型组灌服等体积的生理盐水,干预8周。末次给药后摘取膝关节,通过膝关节病理切片观察各组大鼠软骨组织病理改变;采用RT-PCR法对各组大鼠软骨组织DKK1、WISP1、Wnt1、β-catenin和LRP5 mRNA的表达水平进行对比分析;通过Western blot法检测各组大鼠软骨组织DKK1、WISP1、Wnt1、LRP5和β-catenin的蛋白质含量的变化。结果：与假手术组比较,模型组大鼠关节软骨受损严重,Mankin评分明显升高（P<0.05）;DKK1 mRNA表达水平和蛋白质表达水平明显降低（P<0.05）;WISP1、Wnt1、β-catenin、LRP5 mRNA表达水平及蛋白质表达水平明显升高（P<0.05）。与模型组比较,右归丸高剂量组和硫酸氨基葡萄糖组关节软骨病变明显减轻;Mankin评分明显减轻（P<0.05）;大鼠软骨组织中DKK1 mRNA表达水平和蛋白表达水平明显升高,WISP1、Wnt1、β-catenin、LRP5 mRNA及蛋白表达水平显著降低（P<0.05）。结论：右归丸通过抑制Wnt信号通路中WISP1、Wnt1、β-catenin、LRP5的表达,促进DKK1细胞因子的表达,发挥对KOA的保护作用。     

膝周神经射频热凝治疗顽固性膝骨关节炎疼痛的临床效果

目的:探讨膝周神经射频热凝治疗顽固性膝骨关节炎疼痛的疗效。方法:收集2013年1月至2014年1月,我院收治的顽固性膝骨关节炎疼痛患者62例,随机分为观察组与对照组,各31例。观察组予以膝周神经射频热凝联合关节腔内注射玻璃酸钠治疗,对照组单纯行关节腔内玻璃酸钠注射治疗,比较两组的临床疗效。结果:观察组治疗后VAS评分及OKS评分均显著低于对照组(P0.05);两组均未见明显并发症。结论:膝周神经射频热凝辅助治疗顽固性膝关节炎疼痛疗效显著,创伤较小,可促进关节功能的康复,值得推广应用。     

细胞外囊泡在治疗膝骨关节炎中的作用与前景

膝骨关节炎（knee osteoarthritis,KOA）是以关节软骨退变为主要病变的退行性疾病。目前,KOA尚无有效治疗药物。细胞外囊泡（extracellular vesicles,EVs）是由细胞释放的脂质双分子层包绕形成的球状膜性囊泡,可在细胞间传递核酸、蛋白质等生物活性分子。与动物来源EVs相比,植物来源EVs因其来源广泛且经济,在药物载体递送研究领域引起广泛关注。通过基因工程等方法改造EVs进行药物递送,可极大提高药物递送效率及其疗效。本文综述了动、植物两种来源的EVs在KOA中的治疗进展,特别聚焦于工程化EVs作为药物递送载体在KOA治疗中的研发现状,旨在为利用EVs治疗KOA提供参考。     

人膝骨关节炎软骨下骨OPN的表达及其意义

目的：通过检测人膝骨关节炎裸露软骨下骨中OPN的表达,探讨OPN在OA发病及病情进展中的意义。方法：选取接受膝关节置换手术的膝关节骨关节炎患者软骨下骨标本50例,采用综合评分法对OA患者进行严重程度分级,分为轻、中、重度三组,取正常膝关节软骨下骨（股骨髁关节面）10例作为正常软骨下骨对照;对标本进行免疫组织化学染色,用SPSS17．0统计软件包分析各组间OPN表达的差异及OA患者OPN表达与综合评分、K-L分期的相关性。结果：人膝骨关节炎裸露软骨下骨OPN表达明显高于正常软骨下骨组,差异有统计学意义（P〈0．01）;OPN在轻、中、重度膝骨关节炎裸露软骨下骨的表达差异有统计学意义（P〈0．05）;膝骨关节炎裸露软骨下骨OPN的表达与骨关节炎的综合评分、K—L分期呈正相关。结论：OA患者膝关节软骨下骨OPN表达与疾病严重程度呈正相关,提示OPN在骨关节炎发病及病情进展中可能起作用。     

人膝骨关节炎软骨下骨OPN的表达及其意义

目的:通过检测人膝骨关节炎裸露软骨下骨中OPN的表达,探讨OPN在OA发病及病情进展中的意义。方法:选取接受膝关节置换手术的膝关节骨关节炎患者软骨下骨标本50例,采用综合评分法对OA患者进行严重程度分级,分为轻、中、重度三组,取正常膝关节软骨下骨(股骨髁关节面)10例作为正常软骨下骨对照;对标本进行免疫组织化学染色,用SPSS 17.0统计软件包分析各组间OPN表达的差异及OA患者OPN表达与综合评分、K-L分期的相关性。结果:人膝骨关节炎裸露软骨下骨OPN表达明显高于正常软骨下骨组,差异有统计学意义(P<0.01);OPN在轻、中、重度膝骨关节炎裸露软骨下骨的表达差异有统计学意义(P<0.05);膝骨关节炎裸露软骨下骨OPN的表达与骨关节炎的综合评分、K-L分期呈正相关。结论:OA患者膝关节软骨下骨OPN表达与疾病严重程度呈正相关,提示OPN在骨关节炎发病及病情进展中可能起作用。     

富血小板血浆注射治疗在膝骨关节炎中的应用进展

富血小板血浆(platelet-rich plasma,PRP)由于富含多种活性生长因子,能够刺激软骨细胞增殖,促进软骨前体细胞增殖、迁移、向软骨细胞分化,促进胶原蛋白合成以及抑制软骨的炎性反应和退变,提供有利于组织修复的内环境,延缓病情进展。近年来PRP注射治疗已成为治疗与骨关节炎(osteoarthritis,OA)相关疾病的新型选择,并且疗效显著。为了进一步提高其效用,PRP注射治疗不仅在关节腔内进行,还可在软骨下骨内进行注射。软骨下骨的病变会加速软骨损耗,故有必要将软骨下骨也当作OA众多发病机制和病理过程的关键因素之一。根据PRP的生物特效以及PRP注射治疗在膝骨关节炎(knee osteoarthritis,KOA)中应用的研究进展进行了综述,同时对软骨下骨内PRP注射治疗KOA的研究进行了展望,以期为KOA的治疗提供更加有效的方法。     

仙灵骨葆胶囊联合透明质酸钠对膝骨关节炎患者关节功能、炎症因子及生活质量的影响

目的:观察仙灵骨葆胶囊联合透明质酸钠对膝骨关节炎(KOA)患者关节功能、炎症因子及生活质量的影响,为临床用药提供依据。方法:选取我院骨科于2014年12月-2016年12月间收治的72例KOA患者作为研究对象。采用随机数字表法将患者分为透明质酸钠组(采用透明质酸钠治疗,n=36)和联合组(采用仙灵骨葆胶囊与透明质酸钠联合治疗,n=36)。检测并比较两组患者治疗前及治疗1个月后的超敏C反应蛋白(hs-CRP)水平、肿瘤坏死因子-α(TNF-α)水平。分别于治疗前、治疗1个月后以及治疗6个月后采用生活质量调查表(SF-36)中文版评价患者生活质量,同时采用视觉模拟评估法(VAS)以及膝关节功能评定量表(Lysholm)对膝关节功能进行综合评定。治疗结束后随访半年,观察患者不良反应发生情况。结果:治疗1个月后,两组患者hs-CRP、TNF-α水平均明显下降,且联合组患者hs-CRP、TNF-α水平明显低于透明质酸钠组患者(P0.05)。两组治疗6个月后的VAS评分明显低于治疗1个月后的VAS评分,Lysholm评分均明显高于治疗1个月后的Lysholm评分(P0.05)。治疗1个月后和治疗6个月后,联合组患者VAS评分均明显低于透明质酸钠组患者同期VAS评分,而Lysholm评分均明显高于透明质酸钠组患者同期Lysholm评分(P0.05)。两组治疗6个月后SF-36量表各维度评分均高于治疗1个月后的评分(P0.05)。联合组患者治疗1个月后及治疗6个月后的躯体功能、躯体角色功能、躯体疼痛、总体健康、社会功能和心理健康评分均明显高于透明质酸钠组(均P0.05)。两组均无严重不良反应发生,且不良反应发生情况无明显差异(P0.05)。结论:仙灵骨葆胶囊联合透明质酸钠治疗膝骨关节炎对患者炎症反应、关节功能及生活质量有持续的改善作用,同时安全可靠,值得推广应用。     

全膝关节置换术治疗骨关节炎

目的 探讨人工全膝关节置换术治疗骨关节病的临床疗效。方法 对31例人工全膝关节置换术进行临床分析和总结,并应用HSS膝关节评分系统进行分析。结果 手术优良率为93．6％,患者术后在疼痛、功能及关节活动度等方面都有明显改善。结论 全膝关节置换术是治疗骨关节病的有效方法。     

Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats

Knee osteoarthritis (OA) is a chronic disease that causes pain and gradual degeneration of the articular cartilage. In this study, MIA‐induced OA knee model was used in rats to test the effects of the photobiomodulation therapy (PBM). We analyzed the inflammatory process (pain and cytokine levels), and its influence on the oxidative stress and antioxidant capacity. Knee OA was induced by monosodium iodoacetate (MIA) intra‐articular injection (1.5 mg/50 μL) and the rats were treated with eight sessions of PBM 3 days/week (904 nm, 6 or 18 J/cm²). For each animal, mechanical and cold hyperalgesia and spontaneous pain were evaluated; biological analyses were performed in blood serum, intra‐articular lavage, knee structures, spinal cord and brainstem. Cytokine assays were performed in knee, spinal cord and brainstem samples. The effects of the 18 J/cm² dose of PBM were promising in reducing pain and neutrophil activity in knee samples, together with reducing oxidative stress damage in blood serum and spinal cord samples. PBM improved the antioxidant capacity in blood serum and brainstem, and decreased the knee pro‐inflammatory cytokine levels. Our study demonstrated that PBM decreased oxidative damage, inflammation and pain. Therefore, this therapy could be an important tool in the treatment of knee OA.     

Upregulation of microRNA-27a inhibits synovial angiogenesis and chondrocyte apoptosis in knee osteoarthritis rats through the inhibition of PLK2

The function of microRNA-27a (miR-27a) on synovial angiogenesis and chondrocyte apoptosis in rats with knee osteoarthritis (KOA) by targeting PLK2 is explored in this present study. The rat model of KOA was conducted by anterior cruciate ligament transection. Rats were injected with miR-27a mimics, mimics NC, pcDNA3.1-PLK2 pcDNA3.1, or RLK2 RNAi plasmid via tail vein. A series of assays were used to figure out the functions of miR-27a and PLK2 in synovial angiogenesis and chondrocyte apoptosis in rats with KOA. Furthermore, the putative binding site between miR-27a and PLK2 was determined. Downregulated miR-27a was found in synovial tissues and cartilage tissues of KOA rats. Upregulated miR-27a and downregulated PLK2 inhibited synovial injury and promoted apoptosis of synovial cells, inhibited synovial angiogenesis, inhibited cartilage injury and chondrocyte apoptosis, inhibited cartilage collagen destruction, and alleviates inflammatory injury of synovial tissue and cartilage tissue in KOA rats. Overexpression of PLK2 reverses the effect of upregulation of miR-27a on synovial angiogenesis and chondrocyte injury in KOA rats. Our study suggests that upregulation of miR-27a inhibits synovial angiogenesis and chondrocyte apoptosis in KOA rats through the inhibition of PLK2.     

Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-alpha gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-alpha gene haplotype may be associated with primary knee OA, and genetic variations in the ER-alpha gene may be involved in OA.     

Associations of educational attainment,occupation and community poverty with knee osteoarthritis in the Johnston County (North Carolina) osteoarthritis project

Introduction  

The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA.     

Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis

Osteoarthritis is mediated by various types of cytokines, growth factors, and inflammatory factors that the role of the interleukin-17 family in this disease is becoming increasingly apparent. The aim of this study is to determine the association between the common polymorphisms of IL17A (including rs2275913) and IL17F (including rs2397084 and rs763780) genes with the knee osteoarthritis risk which was followed by a bioinformatics approach. In a case-control study, 254 participants consisting of 127 healthy individuals and 127 subjects with knee osteoarthritis referring to Shahid Beheshti Hospital dependents on Kashan University of Medical Sciences (Kashan, Iran) were enrolled. After samples collection, the polymorphisms genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Finally, some bioinformatics tools were used to analyze the molecular effects of the three studied polymorphisms. Data analysis showed a significant association between rs2275913-GA genotype and the decreased risk of knee osteoarthritis (OR = 0.57, 95% CI = 0.33-0.97, P = .040). However, rs763780-AG genotype (OR = 2.29, 95%CI = 1.11-4.69, P = .024) and rs763780-G allele (OR = 2.01, 95% CI = 1.09-3.72, P = .026) were associated with an increased risk of knee osteoarthritis. However, no significant associations were found between the rs2397084 polymorphism and knee osteoarthritis risk. Our structural analysis revealed that the rs2275913 polymorphism could create a new binding site for TFII-I at the promoter region of IL17A. Also, rs2397084 and rs763780 could significantly affect the function and structure of IL17A. Based on our findings, rs2275913 and rs763780 could be considered as protective and risk factors for knee osteoarthritis, respectively. Therefore, these polymorphisms can be considered as biomarkers for the screening of knee osteoarthritis susceptible persons.     

帕瑞昔布对骨关节炎大鼠软骨细胞的影响

目的:探究帕瑞昔布对骨关节炎大鼠软骨细胞形态、数量及TNF-α/NF-κB信号通路在其中的作用。方法:将所选取的大鼠随机分组,第一组,模型组(MO组):该组大鼠制作骨关节炎大鼠模型;第二组,假手术组(SS组):该组大鼠在骨关节做切口后不做任何处理;第三组,治疗组(TR组):该组大鼠制作骨关节炎模型后给予帕瑞昔布进行治疗,每组5只。通过cck-8法、Western blot法、qRT-PCR法、HE染色法、OARSI评分分别检测三组大鼠软骨细胞增殖情况、TNF-α/NF-κB的蛋白表达、TNF-α/NF-κB mRNA的表达水平、软骨组织病变程度。结果:与SS组大鼠比较,MO组和TR组关节软组织细胞增殖虽然均显著减少(P<0.05),但TR组的增殖显著高于MO组。同样TR组的软骨组织结构好于MO组,OARSI评分显著低于MO组(P<0.05);与SS组大鼠比较,MO组和TR组大鼠TNF-α和NF-κB的蛋白与基因表达水平虽然均显著高于SS组,但TR组的相应蛋白与基因表达水平显著低于MO组(P<0.05)。结论:帕瑞昔布可能通过抑制TNF-α/NF-κB信号通路的表达对骨...     

Biomechanical mechanism of lateral trunk lean gait for knee osteoarthritis patients

The biomechanical mechanism of lateral trunk lean gait employed to reduce external knee adduction moment (KAM) for knee osteoarthritis (OA) patients is not well known. This mechanism may relate to the center of mass (COM) motion. Moreover, lateral trunk lean gait may affect motor control of the COM displacement. Uncontrolled manifold (UCM) analysis is an evaluation index used to understand motor control and variability of the motor task. Here we aimed to clarify the biomechanical mechanism to reduce KAM during lateral trunk lean gait and how motor variability controls the COM displacement. Twenty knee OA patients walked under two conditions: normal and lateral trunk lean gait conditions. UCM analysis was performed with respect to the COM displacement in the frontal plane. We also determined how the variability is structured with regards to the COM displacement as a performance variable. The peak KAM under lateral trunk lean gait was lower than that under normal gait. The reduced peak KAM observed was accompanied by medially shifted knee joint center, shortened distance of the center of pressure to knee joint center, and shortened distance of the knee–ground reaction force lever arm during the stance phase. Knee OA patients with lateral trunk lean gait could maintain kinematic synergy by utilizing greater segmental configuration variance to the performance variable. However, the COM displacement variability of lateral trunk lean gait was larger than that of normal gait. Our findings may provide clinical insights to effectively evaluate and prescribe gait modification training for knee OA patients.     

Effect of severity of knee osteoarthritis on the variability of gait parameters

Gait analysis has provided important information concerning gait patterns and variability of gait in patients with knee osteoarthritis (OA) of varying severity. The objective of this study was to clarify how the variability of gait parameters is influenced by the severity of knee OA. Gait analysis was performed at three different controlled walking speeds in three groups of subjects with varying degrees of knee OA (20 healthy subjects with no OA and 90 patients with moderate or severe OA). The variability of gait parameters was characterized by the coefficient of variance (CV) of spatial-temporal parameters, as well as by the mean coefficient variance (MeanCV) of angular parameters. Based on our results, we conclude that the complexity of gait decreases if the walking speed differs from the self-selected speed. In patients with knee OA, the decreased variability of angular parameters on the affected side represents decreased joint flexibility. This leads to decreased consistency in movements of the lower limbs from stride-to-stride, as shown by increased variability of spatial-temporal parameters. Decreased joint flexibility and consistency of movement can be associated with decreased complexity of movement. Other joints of the kinetic chain, such as joints of the non-affected side and the pelvis, play an important role in compensation and adaptation of step-by step motion and in the ability of secure gait. Results suggest that the variability of gait associated with knee osteoarthritis is gender-dependent. During rehabilitation, particular attention must be paid to improving gait stability and proprioception and gender differences should be taken into account.