股骨头坏死关节软骨金属蛋白酶的表达

目的 探讨金属蛋白酶在股骨头坏死过程中导致关节软骨破坏的作用。方法 临床上采集激素性股骨头坏死、原发性髋关节骨性关节炎及新鲜股骨头／颈骨折患者股骨头关节软骨，切片后进行免疫组化检测MMP-1、MMP-13及TIMP-1的表达。结果 股骨头坏死、原发性髋关节骨性关节炎关节软骨均有较强的MMP-1、MMP-13表达及TIMP-1较低水平的表达。结论 金属蛋白酶在股骨头坏死关节软骨的破坏过程中起着重要的作用。     

外源性透明质酸钠对骨性关节炎患者的血清及关节滑液中基质金属蛋白酶-9的影响

骨性关节炎（osteoarthritis,OA）是一组以关节软骨退变为主要病理特征的临床综合征,其发病原因至今尚不清楚。软骨细胞赖以生存的细胞外基质（extracellular matrix,ECM）的合成与降解失衡是导致软骨退变的重要原因之,许多研究表明基质金属蛋白酶家族（matrix metalloproteinases,MMPs）在这一过程中起重要作用.对于甲、中期的OA患者,     

MMP-12在类风湿关节炎中和骨性关节炎中的研究

目的基质金属蛋白酶(matrix metalloproteinase，MMPs)是分解细胞外基质的重要因子。人类金属弹性蛋白酶(human metallolastase，MMP-12)是MMPs的一种。现已证实由巨噬细胞分泌MMP-12的异常表达与许多疾病有关，如类风湿性关节炎(rheumatoid arthritis，RA)、骨性关节炎(osteoarthritis，OA)等。试验的目的是研究RA和OA病变中MMP-12在滑膜组织中的表达。方法滑膜组织取自临床确诊的22例RA及29例OA患者(均为膝或髋关节置换手术患者)，用免疫组织化学方法进行分析。结果免疫组化染色显示，表达MMP-12的细胞主要为滑膜层细胞．且大部分为炎性巨噬细胞。结论来源于巨噬细胞的MMY-12在RA病变发展，如关节破坏过程中起重要作用，抑制MMP-12高活性可能会为治疗RA提供一种新的途径。     

基质金属蛋白酶3在类风湿关节炎中的表达及调控

类风湿关节炎是一个病因未明的、以慢性关节滑膜炎症和进展性关节破坏为主要表现的自身免疫性疾病。其早期关节改变是滑膜细胞增生和新生血管形成,最终导致局灶性、关节旁和系统性骨丢失。基质金属蛋白酶是一种能降解细胞外所有基质的锌蛋白酶,研究发现,类风湿关节炎患者血清基质金属蛋白酶3(MMP-3)对细胞外间质的降解和关节骨及软骨的破坏均发挥着重要作用,是系统性的炎症标志物,可作为类风湿关节炎特别是早期患者滑膜损害和预后的指标,同时也是评价抗风湿药物治疗疗效的重要指标。因此,本文主要从MMP-3的结构、功能及表达调控方面作一综述,以期对类风湿关节炎的发病机理作进一步的探讨。     

MicroRNA在骨性关节炎中的研究进展

骨性关节炎(OA)是伴随疼痛和关节运动障碍的一种以关节软骨退变和关节周围形成骨质增生为病理特征的慢性进行性骨关节病,临床治疗往往不能令人满意。近年来,MicroRNA(miRNA)在疾病发生发展过程中的作用已成为研究的热点。miRNA是一种非编码的小分子RNA,在基因的表达调控过程中起着非常重要的作用,其常规作用方式是通过与靶基因的3'UTR结合抑制靶基因的表达。目前,已有研究表明miRNA在OA的发病机制过程中有所表达并具有调控降解和修复等作用,改变相关miRNA的表达水平能对其起到治疗作用。本综述总结了miRNA的生物活性及其在骨性关节炎中的具体作用及调节机制,认为miRNA在骨性关节炎的发病机制中起重要作用,在治疗中具有重要的潜在价值,为骨性关节炎的防治提供了一种新的思路。     

IL-22及RANKL在骨性关节炎患者中的表达及调节关系

目的 探究骨性关节炎患者体内细胞核因子-κB受体活化因子配体（Receptor activator of nuclear factor-κB ligand,RANKL）和白介素-22(Interleukin-22,IL-22)的表达差异和调节作用以及在骨性关节炎进程中诱导关节软骨退化的可能机制。方法 采用酶联免疫法检测骨性关节炎患者与正常人血清、关节液中的RANKL和IL-22;番红O-固绿复染观察骨性关节炎患者和正常人关节软骨的组织学改变,免疫组化检测关节软骨中RANKL和IL-22的表达情况;RT-PCR检测骨性关节炎患者和正常人关节软骨组织中RANKL、IL-22和基质金属蛋白酶3(Matrix metalloproteinase-3,MMP-3)等基因的表达水平;蛋白质印迹法检测骨性关节炎患者和正常人关节软骨中RANKL、IL-22和MMP3蛋白的含量。用不同浓度的重组人IL-22(Recombinant human IL-22,rhIL-22)处理体外培养的骨性关节炎患者和正常人的关节软骨细胞,采用RT-PCR检测干预后软骨细胞RANKL和MMP-3基因的表达水平。结果 骨性...     

膝骨关节炎基因表达及中医药干预机制的研究进展

膝骨关节炎(knee osteoarthritis,KOA)是一种多发于中老年的关节退行性的、不可逆转的骨关节病,在人群中的患病率呈不断上升趋势。近年来研究发现,基因点突变和多种基因改变可能导致膝骨性关节炎的高发,中医药干预后能有效影响相关基因改变。笔者通过综述近年来中医药在基因方面对膝骨关节炎的影响研究进展,以期找到防治膝骨关节炎的新靶点和新途径。     

槲皮素治疗类风湿关节炎的作用机制探讨

目前,治疗类风湿关节炎的优选策略是控制炎症与其他病理反应,缓解其疼痛不适等临床症状。槲皮素具有抑制炎症介质的表达和分泌、抗氧化、免疫调节、抑制基质金属蛋白酶的生成,以及抑制滑膜细胞增生等多种生物活性,可抑制类风湿关节炎的病理进程。槲皮素在预防和治疗类风湿关节炎上具有广阔的应用和发展前景。     

老年膝关节骨陛关节炎的社区支持与护理干预

膝关节骨性关节炎（简称膝OA）是以关节软骨病变为主要病理特征的临床综合征，主要表现为膝关节的疼痛和功能不同程度的障碍。作者自2007年1月起通过社区支持与护理干预对65例老年膝关节骨性关节炎进行治疗，取得了满意的疗效。     

老年膝关节骨性关节炎的社区支持与护理干预

膝关节骨性关节炎(简称膝OA)是以关节软骨病变为主要病理特征的临床综合征,主要表现为膝关节的疼痛和功能不同程度的障碍.作者自2007年1月起通过社区支持与护理干预对65例老年膝关节骨性关节炎进行治疗,取得了满意的疗效.     

补肾健骨汤对膝关节病患者氧自由基代谢的影响

对５８例膝关节病患者用补肾健汤治疗前后的红细胞超氧化物歧化酶及血清脂质过氧化物含量进行了动态检测。结果：患者治疗前ＳＯＤ活性低于正常，ＬＰＯ含量高于正常。经治疗病情好转者其氧自由基代谢指标相应改善，显效者恢复正常，无效者仍异常。     

Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis

STUDY OBJECTIVES: To study prognostic value of different biochemical markers for morphological progression of early knee osteoarthritis. DESIGN: A total of 89 patients with knee osteoarthritis (OA) were enroled into the study. The follow-up period was 2 years. Radiological OA progression was evaluated by measuring joint space width. Pentosidine was detected using the HPLC method described earlier, cartilage oligomeric matrix protein (COMP) using the method published by our team. MMP-9, tissue inhibitors of metalloproteinases (TIMP), YKL-40 and hyaluronic acid were detected using commercially available kits. RESULTS: In the group of patients suffering from knee OA, higher serum levels of pentosidine (P=0.04), MMP-9 (P=0.02), TIMP (P=0.04) and COMP (P=0.05) were detected compared with healthy control subjects. Using a correlation analysis method, it has been found that the patients with higher basic serum levels of hyaluronic acid had a faster radiological progression (r=0.56, P<0.005), as well as the patients with higher basic serum pentosidine levels (r=0.30, P<0.005). Other biochemical markers had no statistically significant prognostic value. CONCLUSIONS: In our study, serum levels of hyaluronic acid and pentosidine had a predictive value for further development of knee OA in that further joint space narrowing was detected in the patients with knee OA in the next 2 years.     

氧化应激调控MAPK信号通路与骨关节炎治疗研究进展

骨关节炎(osteoarthritis, OA)是一种常见的中老年慢性疾病，其发病原因与多因素相关，病理表现为软骨、软骨下骨的破坏以及滑膜炎症，以关节疼痛为主要症状。尽管OA的诊疗已逐步完善，但其病理生理机制尚未完全清楚。氧化应激状态下活性氧类(ROS)对软骨内环境稳态有着重要影响，与OA的发生发展有着密切关系。促分裂原活化的蛋白激酶(MAPK)信号通路是介导OA病情进展的最重要的信号通路，该信号通路过表达可以激活多种炎性因子，促进软骨细胞与基质降解，加速OA的发生发展。研究表明MAPK信号通路对OA的调控作用受到ROS水平的影响。因此，通过抑制机体氧化应激降低MAPK信号通路相关因子的表达可以起到治疗OA的作用，为OA的治疗提供新方向和研究思路。     

Osteoarthritis year 2010 in review: imaging

Osteoarthritis (OA) is no longer viewed as a passive, degenerative disorder, but rather an active disease process driven primarily by mechanical factors. OA should also be conceptualized as a disease of a whole joint organ, and therefore imaging of OA requires techniques which enable us to visualize the whole joint organ. Although clinical decision making based on imaging findings remains controversial the importance of imaging-derived data in OA research cannot be overemphasized. Since mid-2009, numerous publications reporting on imaging-oriented studies on OA have been reported. These include magnetic resonance (MR) imaging of numerous features of the whole joint such as synovitis, subchondral bone, meniscus, cartilage and cyst-like lesions. Active research is also ongoing using conventional radiography with a focus on measurements of joint space width and alignment of the knee joint. Ultrasound is emerging as a useful imaging technique, particularly in the field of hand OA research. As the importance of imaging-derived data increases, all potential authors are advised that they should seek opinions from expert musculoskeletal radiologist to ascertain the application of correct imaging techniques, especially the MR pulse sequences and image interpretation. The peer-review process of OA imaging in any journal, therefore, should involve musculoskeletal radiologists experienced in OA research to ensure the publication of papers with scientifically sound contents.     

Current concepts in intraosseous Platelet-Rich Plasma injections for knee osteoarthritis

Knee osteoarthritis (OA) is a degenerative process that slowly destroys the joints producing pain and loss of function, and diminishes the quality of life. Current treatments alleviate this symptomatology but do not stop the disease, being total knee arthroplasty the only definitive solution. Among the emerging treatments, Platelet-Rich Plasma (PRP) has shown promising results in the treatment of OA. However, to improve its effectiveness, it is necessary to approach this pathology targeting the whole joint, not only the cartilage, but including other tissues such as subchondral bone. The pathological processes that occur in the subchondral bone have influence of the cartilage loss, aggravating the disease. The combination of intraarticular infiltrations with intraosseous infiltrations regulates the biological processes of the tissues, reducing the inflammatory environment and modulating the overexpression of biomolecules that generate an aberrant cellular behavior. Although the first clinical results using this technique are promising, further research and developing adequate protocols are necessary to achieve good clinical results.     

Transcriptomic analysis of synovial extracellular RNA following knee trauma: A pilot study

Traumatic knee injuries often result in damage to articular cartilage and other joint structures. Such trauma is a strong risk factor for the future development and progression of osteoarthritis (OA). The molecular mechanisms and signaling pathways modulating response to knee joint trauma remain unclear. Moreover, investigations of biomarkers influencing responses have been targeted rather than broad, unbiased discovery studies. Herein, we characterize the complete complement of extracellular RNA (exRNA) in the synovial fluid of 14 subjects following knee injury. Fluid was collected during surgery from the injured knees, and from the contralateral knee in a subset, undergoing surgical repair of the ACL and/or meniscal repair/debridement. Arthroscopic grading of chondral damage in four knee compartments was performed using the Outerbridge classification. exRNA was extracted and subjected to massively parallel total RNA sequencing. Differential abundance of RNA was calculated between the subject cohorts of injured and non‐injured knee, average Outerbridge score ≥0.5 and less, and chronic and acute injury duration defined as ≤4 months till surgery or longer. Overall, expression of several thousand genes was identified in the synovial fluid. Furthermore, differential expression analysis suggests a role of exRNA fragments of matrix metalloproteinases and skeletal muscle fiber genes in the response to traumatic injury. Together, these data suggest that high‐throughput approaches can indicate exRNA molecular signatures following knee trauma. Future studies are required to more fully characterize the biological roles of these exRNA and the cadence of their respective release that may lead to translational treatment options for post‐traumatic OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1659–1665, 2018.

     

Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity

OBJECTIVE: Although available nonsurgical pharmacotherapies for treatment of osteoarthritis (OA) are considered to be solely symptom-modifying agents, recent advances have been made in the search for agents that may modify disease progression. Intra-articular hyaluronan (HA) therapy is one symptom-modifying approach that has been found to be safe and effective for reducing pain due to OA of the knee. Presented here is a review of the evidence that HAs may also modify the rate of OA disease progression in addition to providing symptomatic efficacy. DESIGN: A review of the literature based on a MEDLINE search through June 2004, using the terms HA, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20, OA, disease modification, structure modifying and joint structure. RESULTS: Evidence for disease-modifying activity of HAs stems from 1) the complex biochemical effects of HAs in the synovium and extracellular matrix of the articular cartilage, including interactions between exogenously administered HA and articular cartilage, subchondral bone, matrix proteoglycans, and collagens; 2) the effects of HA administration in animal models of OA, including total or partial meniscectomy and anterior cruciate ligament transectomy; 3) results of clinical trials using one HA, Hyalgan (sodium hyaluronate, molecular weight 500-730 kDa) that evaluated structural outcomes, such as joint-space width, chondrocyte density and vitality, and arthroscopic evaluation of chondropathy. DISCUSSION: Growing preclinical and clinical evidence supports the notion that, in addition to relieving the symptoms of OA, HAs also modify the structure of the diseased joint and the rate of OA disease progression, at least early in the evolution of the disease process.     

The protective effect of OP-1 on articular cartilage in the development of osteoarthritis

OBJECTIVE: The purpose of this study was to determine whether osteogenic protein 1 (OP-1) would protect articular cartilage from degeneration during the development of osteoarthritis (OA) in the rabbit anterior cruciate ligament transection (ACLT) model. Previous studies have shown that OP-1 is vital to cartilage matrix integrity and repair, stimulates synthesis of cartilage matrix components, proteoglycans, and collagen, and has a protective effect against catabolic mediators like matrix metalloproteinases and interleukin-1. METHODS: The rabbit ACLT model was used in which the anterior cruciate ligament was transected leading to OA. OP-1 was delivered to the joint surgically for approximately 6 weeks by implantation of an Alzet osmotic pump into the medial thigh with a catheter threaded from the pump into the knee joint. Forty rabbits (20 control and 20 experimental) had the ACLT surgery and implantation of the pump performed simultaneously. They were sacrificed after 9 weeks for analysis. The OA was graded using the Outerbridge classification with India Ink staining. Histological staining and histomorphometry with Hematoxylin & Eosin and Safranin O were performed to analyze OA progression and semi-quantitative polymerase chain reaction (PCR) was performed for anabolic and catabolic genes. RESULTS: The experimental group had an average Outerbridge score of 1.8 vs 2.5 for the controls (P<0.05). Histomorphometry showed 10.9% surface deterioration or an average depression of 0.05mm vs 22.3% and 0.1mm for the controls (P<0.05). Semi-quantitative PCR showed a significantly greater expression of aggrecan and collagen type II in the OP-1 treated cartilage when compared to controls and less expression of aggrecanase, a catabolic mediator. CONCLUSIONS: OP-1 may have a potential benefit in protecting articular cartilage during the development of OA.     

Static knee alignment and its association with radiographic knee osteoarthritis

OBJECTIVES: Although knee alignment is associated with the progression of knee osteoarthritis (OA), it is unclear which features that characterize radiographic OA are related to alignment. The aim of this study was to examine the relationship between static knee joint alignment (measured as a continuous variable) and the radiographic features of knee OA (joint space narrowing and osteophytes). METHODS: One hundred and twenty one adults with symptomatic knee OA were recruited using a combined strategy including referral from specialist centres, arthritis support groups and media advertising. X-rays were performed to classify the severity of disease and to determine static knee alignment. RESULTS: Increasing varus knee alignment was associated with increasing risk of medial compartment joint space narrowing (P < 0.001) and osteophytes (P = 0.005). Increasing valgus knee alignment was associated with an increased risk for lateral compartment joint space narrowing (P < 0.001) and osteophytes (P = 0.002). CONCLUSION: This study has demonstrated that the static knee angle, measured as a continuous variable, is an important determinant of the compartment-specific features of radiographic knee OA. Further work is required to determine whether interventions aimed at correcting these relatively minor levels of varus and valgus angulation will have an effect on the risk of tibiofemoral OA.     

早期膝骨关节炎的划分

膝骨关节炎(OA)是1种慢性退行性病变,随着病变不断进展,整个关节结构会逐渐发生不可逆的改变,最终导致关节功能破坏和残疾。目前尚无特效的治疗方法完全阻断OA的进展,临床发现并确诊OA时,常常是中晚期阶段,继之的预防及治疗也存在延迟。因此,如果能划分早期OA,也就是说在更多组织发生不可逆性病变前,早期发现OA,就有可能对OA进行更好地预防和治疗,并评估治疗方法,进而提高患者的生存质量,降低残疾发生率。本文从临床,X线,病理生理,MRI,关节镜,分子生物标记物等各个方面对如何划分早膝OA及其病变进展进行综述,期望为早期预防和发现OA,进而对OA患者进行早期治疗提供帮助。