关节液抵抗素水平与膝骨关节炎的相关性

目的探讨抵抗素在关节炎患者关节液中的表达水平与关节炎严重程度的相关性。方法选择122例膝关节炎患者,采用X线Kellgren-Lawrence(K-L)分级方法将患者分为Ⅱ级、Ⅲ级和Ⅳ级。采用西安大略和麦马斯特大学骨性关节炎指数(WOMAC)评分系统评价各组患者膝关节临床症状严重程度,通过关节镜直视下采用Noyes评分评估关节软骨病变程度。采用双抗夹心酶联免疫吸附法检测关节滑液中抵抗素与Ⅱ型胶原基端端肽(CTX-Ⅱ)水平,以评估其与膝骨关节炎严重程度的相关性。结果各组膝骨关节炎患者关节滑液中抵抗素及CTX-Ⅱ水平差异有统计学意义(P0.05),Ⅳ级患者高于Ⅲ级及Ⅱ级患者。关节液中抵抗素表达水平与X线K-L标准呈正相关(r=0.624,P0.001),与WOMAC量表中疼痛评分(r=0.214,P0.001)、肢体功能评分(r=0.533,P0.001)及总体评分(r=0.491,P0.001)呈正相关,与WOMAC量表中的僵硬评分无相关性(r=0.066,P0.05)。关节炎患者的抵抗素水平分别与关节软骨损伤Noyes评分(r=0.543,P0.001)及关节液中CTX-Ⅱ水平(r=0.411,P=0.001)呈正相关。结论骨关节炎患者关节滑液中抵抗素表达水平与其病变的严重程度呈正相关,检测关节液中抵抗素可有助于早期发现关节炎,并可作为一种评估骨关节炎病变程度的生物标志物。     

类风湿关节炎活动期滑液中葡萄糖6-磷酸异构酶水平及与抗环瓜氨酸肽抗体的关系

目的 检测葡萄糖-6-磷酸异构酶(GPI)在类风湿关节炎(RA)活动期膝关节滑液中的含量,并探讨滑液中GPI与抗环瓜氨酸肽(CCP)抗体的关系.方法 用酶联免疫吸附法(ELISA)检测22例RA活动期患者和37例骨关节炎活动期患者滑液中GPI和抗CCP抗体的浓度.组间比较采用t检验,相关性分析采用Spearman相关分析.结果 RA活动期患者膝关节滑液中的GPI浓度高于骨关节炎活动期患者[(9.6±8.4)和(0.9±1.8)μg/ml],差异有统计学意义(P＜0.01);RA活动期患者与骨关节炎活动期患者滑液的抗CCP抗体浓度分别为(14.61±18.64)和(1.42:±0.09) U/ml,差异有统计学意义(P＜0.01);RA活动期患者膝关节滑液中GPI含量和抗CCP抗体浓度呈正相关(r=0.447,P=0.037).结论 GPI在RA活动期患者滑液中高表达,可能与RA发生发展过程中慢性滑膜炎、骨质破坏有关.GPI与抗CCP抗体呈正相关,两者可作为RA实验室诊断的参考指标.     

基质金属蛋白酶-2和-9在实验性酒精性肝病中的动态变化及表达

目的 动态观察基质金属蛋白酶－2（MMP－2）和－9（MMP－9）在大鼠酒精性肝病发生中的变化及表达。方法 用灌胃的方法制备大鼠酒精性肝病的动物模型;应用免疫组织化学技术检测MMP－2及MMP－9在酒精性肝病中变化和表达。结果 酒精性肝病组MMP－2、MMP－9含量明显高于对照组（P＜0．05）,并且随造模时间延长其含量进行性增加。免疫组织化学可见MMP－2主要位于血管内皮细胞、窦内皮细胞及肝窦细胞的胞浆。MMP－9主要位于静脉周围的肝细胞及肝窦细胞的胞浆中。结论 在大鼠酒精性肝病发生发展中,MMP－2及MMP－9水平进行性增加。     

类风湿关节炎患者滑膜、滑液和血浆中PAI的检测及其临床意义

目的 检测Ⅰ型和Ⅱ型纤深酶原激活物抑制剂（ＰＡＩ－１和ＰＡＩ－２）在类风湿关节炎（ＲＡ）患者滑膜组织中的定位和表达,同时测定ＲＡ患者滑液和血浆中ＰＡＩ－１的含量和活性,并分析其临床意义。方法 运用免疫组织化学方法检测了２４例ＲＡ、１８例骨关节炎（ＯＡ）和６例正常滑膜组织中ＰＡＩ－１和ＰＡＩ－２的定位及其表达;采用ＥＬＩＳＡ双抗体夹心法测定４６例ＲＡ和８例ＯＡ患者血浆、１４例ＲＡ滑液和１２例正常对照     

血脂康对急性冠状动脉综合征患者血清基质金属蛋白酶2和9的影响

目的探讨血脂康对急性冠状动脉综合征患者基质金属蛋白酶2和9的影响。方法30例急性冠状动脉综合征患者住院后服用血脂康,在服药前、服药后7天和30天分别收集静脉血1 mL,以检测基质金属蛋白酶2和9及相应酶原。正常对照组为25例健康自愿者。结果与正常对照组相比,急性冠状动脉综合征患者基质金属蛋白酶2及酶原明显增高(P<0.01)。与服药前相比,服用血脂康后7天基质金属蛋白酶2和9及相应酶原无明显变化,服药30天后基质金属蛋白酶2下降(P<0.05),基质金属蛋白酶2酶原、基质金属蛋白酶9及酶原无明显变化(P>0.05)。结论急性冠状动脉综合征患者血清基质金属蛋白酶2及酶原明显增高,血脂康可以降低基质金属蛋白酶2。     

重型肝炎患者肝组织基质金属蛋白酶-1及其抑制因子-1 mRNA的表达

目的：观察重型肝炎患者基质金属蛋白酶－1（MMP－1）和金属蛋白酶组织抑制因子－1（TIMP－1）mRNA的表达以及胶原蛋白的沉积情况，从胶原降解的角度探讨重型肝炎致肝纤维化的机制。方法：重型肝炎肝组织标本20例，非肝病患者肝组织6例，用原位杂交法检测肝组织MMP－1和TIMP－1 mRNA-1 的表达，并作I、Ⅳ型胶原的免疫组化以及天狼红胶原染色。结果：与对照组比较，重型肝炎组的MMP－1 mRNA和TIMP－1 mRNA表达显著增加，肝组织胶原蛋白总含量和I、Ⅳ型胶原蛋白含量亦显著增加。肝组织胶原蛋白总含量和I、Ⅳ型胶原蛋白含量与MMP－1 mRNA表达无明显相关性，与TIMP－1 mRNA表达呈正相关。结论：重型肝炎患者肝纤维化的发生与金属蛋白酶抑制因子增加、抑制金属蛋白酶的活性、降低间质胶原蛋白的分解有关。     

兔前交叉韧带切断骨关节炎模型中MMP-1 MMP-13及TIMP-1的mRNA表达研究

目的；研究兔膝关节前交叉韧带切断（ACLT）骨关节炎模型关节软骨及滑膜中基质金属蛋白酶（MMP）－1，MMP－13及组织源性基质金属蛋白酶抑制剂（TIMP）－1在不同造模时期 的表达情况，探讨上述因子在骨关节炎（OA）发病过程中的作用。为该模型作OA防治研究提供理论依据。方法：实验组ACLT模型兔20史，分别于造模4周各处死10只，假手术对照组大白兔10只于术后8周处死。解剖显微镜下行股骨髁关节软骨退变的大体评分，取股骨内髁内侧退变软骨及邻近滑膜，用反转录－多聚酶链反应（RT－PCR）的方法检测MP－1，MMP－13及TIMP－1的mRNA表达。结果：ACLT术后4周即可见软骨退变，8周时退变进一步加重（P＜0．02），对照组无明显软骨退变。对照组软骨及滑膜中MMP－1及TIMP－1的检出率较低，造模4周时检出率明显增高（P＜0．05），部分阳性标本表达量有一定增高，造模8周时MMP－1仍有很高的检出率，表达量持续增高，而TIMP－1检出率较4周时下降；MMP－13在对照组滑膜中没有检测出，造模4周时有一定的检出率，8周时检出率明显增加（P＜0．002），软骨 中对照组MPP－13的表达及表达量都很低，造模4周时表达率明显增高（P＜0．05），8周时表达率却明显下降。结论：MMP－1、MMP－13及TIMP－1在骨关节炎软骨退变过程中起重要作用。其中MMP－1在造模4周和8周都有很高的检出率，且从阳性标本的电泳情况看，其表达量逐渐增高，适合作为OA防治研究中的评价指标。     

血管内皮细胞生长因子在骨关节炎患者膝关节滑膜和滑液中的表达及其意义

目的 检测不同阶段的骨关节炎患者膝关节滑膜组织和滑液中血管内皮细胞生长因子(VEGF)的表达情况,评价VEGF作为进展期骨关节炎的标志的可行性。方法 临床收集膝关节镜或关节置换手术患者的滑液和滑膜组织,根据X线平片的K-L分级进行分组。以Kellegren-Lawrence (K-L)分级均为0级的单纯膝关节半月板损伤的患者作为对照组。酶联免疫吸附测定( ELISA)法检测各组滑液中VEGF的含量,免疫组织化学染色方法检测VEGF在滑膜组织中的原位表达。统计学方法采用方差分析。结果 骨关节炎滑膜组织普遍存在不同程度的炎症,滑膜色泽变暗红,组织增生,甚至呈绒毛样改变。免疫组织化学染色显示,VEGF在滑膜衬里层及血管平滑肌细胞表达。2～4组的滑液中VEGF水平逐级增高,从(1181±116)、(1632±140)到(2252±216) pg/ml,明显高于对照组(648±129) pg/ml,差异均有统计学意义（P＜0.01）;免疫组织化学阳性细胞分数对照组和第2～4组分别为(5±4)％和(9±4)％、(16±6)％、(21±6)％,差异有统计学意义(P＜0.01)。结论 关节滑膜产生的VEGF参与了骨关节炎软骨损害的病理过程,滑液中VEGF水平的持续升高可作为判断骨关节炎病情活动的一个指标。     

骨关节炎患者基质金属蛋白酶和转化生长因子-β的检测及其临床意义

骨关节炎 (ＯＡ)为最常见的关节炎 ,其病理特点为关节软骨进行性变性和破坏及骨赘形成。ＯＡ患者关节软骨细胞外基质合成与降解失衡是造成软骨变性的重要原因之一 ,其中基质金属蛋白酶 (ＭＭＰｓ)可能起决定性作用。转化生长因子 β(ＴＧＦ β)影响软骨代谢的机制与促进金属蛋白酶组织抑制因子表达有关。有研究表明 ,ＴＧＦ β是促进ＯＡ软骨修复的机制之一。我们对临床诊断为骨关节炎的患者进行血清ＭＭＰ 9和ＴＧＦ β的测定 ,并与正常人对照 ,探讨ＭＭＰ 9和ＴＧＦ β的临床意义。对象与方法1.对象 :2 0 0 0年 9月～ 2 0 0 2年 1月我院…     

6w高强度跑台运动对大鼠关节软骨和关节滑液中基质金属蛋白酶-1、-3和-9的影响

目的探讨高强度跑台运动对大鼠关节软骨和关节滑液中基质金属蛋白酶(MMP)-1、-3、-9的影响。方法选取30只雌性SD大鼠,随机分成对照组和高强度运动组,每组15只,其中高强度运动组进行6 w高强度跑台运动。6 w后处死所有动物,取大鼠膝关节滑液以及股骨内侧髁软骨组织,HE染色观察软骨病理学改变;酶联免疫吸附法(ELISA)检测大鼠关节滑液中MMP-1、-3和-9蛋白的含量;Western印迹以及实时定量PCR法观察软骨组织中MMP-1、-3、-9蛋白和mRNA的表达。结果高强度运动组大鼠明显出现软骨损伤,并且关节滑液中MMP-1、-3、-9的蛋白水平明显高于对照组(P0.05);关节软骨中MMP-1、-3、-9的蛋白和mRNA水平明显高于对照组(P0.05)。结论高强度运动可导致关节软骨损伤;而关节滑液和关节软骨中MMP-1、-3、-9的高表达很可能是高强度运动致关节软骨损伤的机制之一。     

Levels of Rheumatoid Factor Isotypes, Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinase-1 in Synovial Fluid from Various Arthritides

When synovial effusion is the only symptom, it is often difficult to make an exact diagnosis of the arthritic disease. To distinguish various types of arthritis with synovial effusion, we measured the levels of matrix metalloproteinase-3 (MMP-3, Stromelysin), tissue inhibitor of metalloproteinase-1 (TIMP-1) and rheumatoid factor (RF) isotypes in synovial fluid (SF) from patients with rheumatoid arthritis (RA), osteoarthritis (OA), pyogenic arthritis (PA), pseudogouty arthritis (PG), gouty arthritis (GA) and traumatic arthritis (TA). SF was aspirated from the knee joint or the ankle joint. Levels of IgG-, IgM- and IgA-RF isotypes were measured by ELISA. Levels of MMP-3 and TIMP-1 in SF were simultaneously determined by a one-step EIA system. Levels of IgG-RF, IgM-RF and MMP-3 in SF from RA patients were significantly higher than those in OA, PA, PG, GA and TA. However, IgA-RF in SF from RA patients, when compared with PA and GA, did not show a significantly increased level. In addition, TIMP-1 in SF from RA, when compared with PA and TA, also has not shown a significantly increased level. Therefore, in addition to analysing clinical data, measurements of IgG-RF, IgM-RF and MMP-3 in SF may contribute in distinguishing RA from other arthritic diseases. Received: 18 January 1999 / Accepted: 15 June 1999     

Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis

OBJECTIVE: To examine matrix metalloproteinase 9 (MMP-9) in the synovial fluid (SF) and synovial membrane (SM) in relation to vascular endothelial cell (EC) apoptosis, vascular endothelial growth factor (VEGF), and SM vascular pattern. METHODS: Thirty-four patients underwent needle arthroscopy of the knee joint; 12 had early rheumatoid arthritis (RA), 12 had early psoriatic arthritis (PsA), and 10 had osteoarthritis (OA). The early RA and early PsA patients were matched for disease activity. SF levels of MMP-9 and VEGF were measured by an enzyme-linked immunosorbent assay, and EC apoptosis was measured by TUNEL assay. MMP-9 expression was examined in SM by immunohistochemistry. Synovial tissue explants were stimulated with VEGF, and MMP-9 levels were measured in the supernatants. The synovial vascular pattern was recorded. RESULTS: SF MMP-9 levels were significantly higher in early PsA patients than in early RA patients; OA patients had minimal levels. MMP-9 levels correlated with blood vessel morphology and SF VEGF levels. MMP-9 expression was greater in early PsA SM than in early RA SM, but the difference was not significant. In contrast however, EC apoptosis was greater in early RA SM than in early PsA SM. MMP-9 levels increased 2-fold and 9-fold, respectively, in SM explant culture supernatants on day 7 in response to stimulation with 25 ng/ml and 50 ng/ml of VEGF. CONCLUSION: SF MMP-9 levels correlate with the pattern of SM neovascularization and SF VEGF levels in early inflammatory arthritis, and VEGF increases MMP-9 production by SM. Endothelial cell apoptosis, however, appears to be more prevalent in early RA. This combination of factors may explain the pattern of differential angiogenesis in these arthritides.     

Implication of MMP-9 and urokinase plasminogen activator (uPA) in the activation of pro-matrix metalloproteinase (MMP)-13

We examined whether the expression and activation of pro-matrix metalloproteinase (MMP)-1 varies from that of pro-MMP-13 in the joint fluid of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. To do this, joint fluid was collected from 34 RA and 34 OA patients. The collagenase (pro-MMP-1 and MMP-13, total MMP-1, and MMP-13), gelatinase (total MMP-2 and MMP-9), stromelysin (total MMP-3), matrilysin (total MMP-7), uPA, and tissue inhibitor of MMP (TIMP) levels were measured by ELISA. The level of total MMP-1 in RA joint fluids was similar to that of the OA joint fluid. In contrast, the level of total MMP-13 in the RA group was significantly higher than that of the OA group. Among various MMPs (MMP-2, MMP-3, MMP-7, and MMP-9), only MMP-9 was strongly associated with total MMP-13 in both RA and OA. The level of uPA was also strongly associated with MMP-13 in RA but not OA, while the level of TIMP-1 and TIMP-2 was not significantly different between RA and OA. In conclusion, MMP-9 and uPA might be involved in the activation of pro-MMP-13 through unknown mechanisms in arthritic diseases.     

MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis

OBJECTIVE: To analyse matrix metalloproteinases (MMPs) and tissue inhibitor-1 of MMPs (TIMP-1) levels in the systemic circulation and synovial fluid (SF) of patients with RA and to compare these levels with inflammatory and collagen degradation markers. METHODS: ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/alpha(2)-macroglobulin complexes, and collagen degradation products were measured by sandwich ELISA, activity assays, and HPLC in paired SF and serum samples from 15 patients with RA and 13 with OA. RESULTS: MMPs were higher in SF of patients with RA than in OA or controls. MMP levels in SF of patients with OA were higher than in controls. In serum, levels of proMMP-3, -8 and -9 were higher in patients with RA than in OA or controls, whereas only proMMP-8 and -9 were higher in serum of patients with OA than in controls. A strong correlation was seen between serum and SF levels of MMP-8 and -9 in RA. Increased levels of MMP/alpha(2)-macroglobulin complexes indicated an MMP/TIMP imbalance in serum and SF in RA. SF hydroxyproline correlated significantly with SF levels of proMMP-9 in RA. CONCLUSIONS: Systemic MMP-8 and -9 levels represent the situation in the inflamed joint; MMP-9 is likely to be involved in degradation of joint collagen. The hypothesis of MMP/TIMP imbalance in RA is strengthened.     

Assessment of the clinical significance of gelatinase activity in patients with juvenile idiopathic arthritis using quantitative protein substrate zymography

OBJECTIVE: To measure gelatinase activities in paired synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to assess how these activities relate to clinical and laboratory measures of disease activity. METHODS: A quantitative protein substrate zymography method was adapted and validated for use with serum and SF. Bands of activity were measured by densitometry and correlated with standard laboratory indicators of inflammation: erythrocyte sedimentation rate and platelet count. RESULTS: Gelatinase activity was found consistently in patients with JIA, with reproducible, quantified bands of activity corresponding to pro-matrix metalloproteinase-9 (pro-MMP-9), including the neutrophil associated lipocalin complex, and pro- and active forms of MMP-2. Both active MMP-2 and pro-MMP-9 were higher in JIA serum than in controls, though no differences were seen between patients grouped according to age, disease duration, or JIA subtype. However, SF MMP-9 correlated significantly with the laboratory indicators of inflammation, as did the relative level of active MMP-2. CONCLUSIONS: Both MMP-2 and MMP-9 gelatinolytic activities are raised during active JIA and associated with inflammatory activity regardless of age and disease duration, supporting a role for MMPs in the breakdown of joint components from early in disease. These MMPs may be specific markers of active joint destruction linked to inflammatory JIA, MMP-9 as a product of infiltrating cells, and the activation of MMP-2 produced within the joint.     

Expression levels and association of gelatinases MMP-2 and MMP-9 and collagenases MMP-1 and MMP-13 with VEGF in synovial fluid of patients with arthritis

This study was performed to provide evidence, albeit indirectly, as to which matrix metalloproteinases (MMPs), among the gelatinases MMP-2 and MMP-9 and the collagenases MMP-1 and MMP-13, play a more proactive role in the angiogenic process in arthritic joint. Joint fluid was collected from 33 patients with rhuematoid arthritis (RA) and osteoarthritis (OA), and protein (MMPs and vascular endothelial growth factor (VEGF)) levels were measured by ELISA, and the association of MMPs with VEGF was evaluated in joint fluid of patients with RA or OA. The levels of collagenases (total MMP-1 and total MMP-13) and gelatinases (total MMP-2 and total MMP-9) in RA joint fluid were significantly higher than those in OA fluid. Total MMP-9 levels were significantly associated with VEGF levels in RA fluids, but not in OA fluid, while total MMP-13 levels were strongly associated with VEGF levels in both RA and OA fluid. However, total MMP-2 and total MMP-1 levels were not associated with VEGF levels in either RA or OA joint fluid. Our results indirectly suggest that in RA and OA, MMP-9 and MMP-13 may play a more important role in angiogenesis than MMP-2 and MMP-1.     

Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: relationship to mediators of systemic and local inflammation

OBJECTIVE: To determine in vivo the extent of damage to, and changes in turnover of, articular cartilage type II collagen (CII) and the proteoglycan aggrecan following the onset of inflammatory arthritis in humans, and to examine the hypothesis that there are direct relationships between cartilage biomarkers of damage/turnover and clinical, histologic, and molecular markers of inflammation. METHODS: Synovial fluid (SF) and synovial membrane (SM) were obtained by arthroscopy, and a synovitis score was determined, in 32 patients with rheumatoid arthritis (RA) (13 with early untreated disease, 19 with established disease), 18 with psoriatic arthritis (PsA), and 10 with osteoarthritis (OA). Systemic disease activity markers were recorded, and SM CD3+ T cells, CD4+ T cells, CD68+ macrophages, and lining layer hyperplasia were quantified. SF levels of tumor necrosis factor alpha (TNFalpha), interleukin-10 (IL-10), matrix metalloproteinase 1 (MMP-1), MMP-3, Col2-3/4C(Long mono) neoepitope (C2C) (reflecting collagenase cleavage of cartilage CII), C-propeptide of type II procollagen (PIICP) (a biosynthesis marker), keratan sulfate (KS), and the 846 epitope of aggrecan (turnover) were measured by enzyme-linked immunosorbent assay or radioimmunoassay. RESULTS: Levels of cartilage degradation products in early RA or early PsA were not elevated above levels in OA, although in early inflammatory arthritis, TNFalpha and MMP-1 levels were similar to those observed in late inflammatory disease and higher than those in OA. PIICP was reduced in early RA. Correlations were observed between the SF C2C neoepitope level and the Health Assessment Questionnaire score, C-reactive protein level, plasma viscosity, synovitis score, and SF TNFalpha and MMP-1 levels. KS epitope content was reduced in direct relation to SM macrophage infiltration in the sublining and lining layers and in the presence of elevated SF MMP-3. Both SF MMP-1 and SF MMP-3 levels correlated with CD4+ T cell infiltration and lining layer hyperplasia in the SM, and MMP-1 levels correlated with lining layer CD68 levels, but TNFalpha and IL-10 levels did not. CONCLUSION: Except for CII synthesis, there were no significant changes in extracellular matrix turnover of aggrecan or CII in the early stages of human inflammatory arthritis. However, the direct correlation between the increases in TNFalpha and MMP-1 production and collagen degradation suggests that collagenase cleavage of cartilage collagen is related to the activities of TNFalpha and MMP-1. The reduction in CII synthesis in early RA may contribute to the developing pathology, since a lack of synthesis of this molecule would inhibit maintenance of cartilage matrix.     

Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand

OBJECTIVE: To investigate the relationship between matrix metalloproteinases (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA), and to determine which MMP have a major role in cleaving FasL. METHODS: The concentrations of sFas and sFasL in SF from 48 patients with RA and 43 patients with osteoarthritis (OA) were measured using specific ELISA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measured by ELISA. The active forms of gelatinases were detected by gelatin zymogram. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to investigate whether FasL is cleaved from membrane bound FasL. RESULTS: Significantly higher levels of MMP-1, 3, and 9 were found in SF from RA patients compared to OA patients, but MMP-7 was not detectable in either group. The concentrations of sFas and sFasL in SF were also higher in RA than in OA patients. However, there was no relationship between the concentration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were closely correlated with the level of sFasL and with disease activity of RA. Enzymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL. CONCLUSION: There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate that the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA.     

Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum.

OBJECTIVE: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). METHODS: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. RESULTS: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p < 0.0001, p < 0.0001), and correlated with ESR in all arthritis (r = 0.658, p < 0.0001, r = 0.404, p < 0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727, p < 0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p < 0.01, p < 0.0001, p < 0.001) than those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. CONCLUSION: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA.     

Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis

Objective. To determine the expression of matrix metalloproteinase 9/gelatinase B (MMP-9) in synovial fluid (SF), plasma, and synovial tissue from individuals with rheumatoid arthritis (RA), inflammatory arthritis (IA), and osteoarthritis (OA), using specific monoclonal antibody reagents. Methods. Gelatinolytic activity in the SF and plasma of patients with RA, IA, and OA was assessed by gelatin zymography. A mouse monoclonal antiserum, 277.13, which selectively recognizes soluble latent forms of human MMP-9, was used to quantitate MMP-9 levels in patient synovial effusions, plasma, and synovial tissue with a capture sandwich enzyme-linked immunosorbent assay (ELISA). Fifty-one SF samples (31 RA, 9 OA, 11 IA) were analyzed. Immunolocalization of MMP-9 in RA, OA, and normal synovium was investigated using MMP-9–specific antisera. Results. MMP-9 antigen levels in synovial effusions were elevated 67-fold in RA samples compared with OA samples. In addition, although MMP-9 antigen levels in IA synovial effusions were 2.7-fold less than the values in RA samples, they were elevated 34-fold over the values in OA samples. These data indicate an association between increased MMP-9 levels and inflammatory arthritis. A predominant 92-kd gelatinolytic activity (specifically inhibited by EDTA) was evident in RA and IA samples, but no activity was observed in OA samples. Among 86 plasma samples (17 RA, 9 IA, 60 normal controls) analyzed for MMP-9 antigen levels by immunocapture ELISA, MMP-9 antigen levels were elevated 7-fold in RA plasma compared with normal plasma. RA synovial tissue extracts demonstrated elevated levels of MMP-9 antigen compared with OA synovial tissue. MMP-9 immunolocalization studies demonstrated expression in infiltrating leukocytes (neutrophils and macrophages), endothelial cells, and synovial fibroblasts in RA synovium. Conclusion. Latent MMP-9 and/or MMP-9–tissue inhibitor of metalloproteinases 1 (TIMP-1) complexes are elevated in RA and IA SF compared with OA SF. In addition, MMP-9 is increased in RA plasma versus normal control plasma. Synovial tissue levels of MMP-9 antigen are also elevated in RA versus OA. The tissue distribution of MMP-9 within RA synovium is localized to sites of inflammation comprising surface synovial lining cells, endothelium, and leukocytes. Taken together, these observations suggest that connective tissue turnover occurs as a result of excessive MMP activity over TIMP action in the invading pannus, periarticular tissue, or SF. Further studies such as those used in the present investigation will help elucidate the role of a number of different enzymes and inhibitors in the destructive arthropathies.