MMP-13和MMP-14在脊索瘤中的表达特点及其意义

目的探讨MMP-13和MMP-14蛋白在脊索瘤中的表达及其意义。方法应用组织芯片结合免疫组化方法对47例脊索瘤患者的肿瘤和瘤旁正常组织的MMP-13和MMP-14蛋白表达进行检测。结果 MMP-13和MMP-14在脊索瘤肿瘤组织内阳性表达率分别为82.98%和76.59%,显著高于正常组织中的表达（5.26%和21.05%）。MMP-13与MMP-14阳性表达存在正相关关系。MMP-14蛋白在脊索瘤组织中的阳性表达率与脊索瘤发生的年龄相关。MMP-13、MMP-14蛋白表达阳性的脊索瘤患者较MMP-13、MMP-14蛋白表达阴性者的无瘤生存期短。结论 MMP-13和MMP-14蛋白表达改变可能与脊索瘤的发生机制有关,也可促进脊索瘤的侵袭性生长。MMP-13、MMP-14蛋白是影响脊索瘤预后的重要因素。     

MMP-3和TIMP-3在膀胱移行细胞癌中的表达及意义

目的 研究基质金属蛋白酶3(MMP-3)及其抑制物组织基质金属蛋白酶抑制剂3(TIMP-3)在膀胱移行细胞癌中的表达及其临床意义.方法 通过免疫组化Elivision法检测48例膀胱移行细胞癌组织及20例正常膀胱组织中的MMP-3和TIMP-3的表达.结果 MMP-3和TIMP-3在正常膀胱组织中不表达,随着肿瘤分级和分期的增高,MMP-3表达增高,但差异无统计学意义(P＞0.05).TIMP-3表达降低,但在肿瘤分级中差异有统计学意义(P＜0.05).结论 MMP-3的高表达,TIMP-3的低表达与膀胱移行细胞癌的恶性程度有关,在膀胱移行细胞癌的发生发展中起重要作用,可作为临床判断膀胱移行细胞癌的恶性程度及预后的重要参考指标.     

MMP-3在退变腰椎间盘组织中的表达及意义

目的研究MMP-3在退变腰椎间盘髓核和纤维环组织中的表达及其临床意义。方法用半定量RT—PCR和免疫组织化学法检测实验组1（30例退变腰椎间盘髓核）、实验组2（30例退变腰椎间盘纤维环）和对照组（10例创伤腰椎间盘髓核）中MMP3mRNA和蛋白表达。结果实验组1MMP-3mRNA和蛋白的表达均显著高于对照组（P均〈0．01）,实验组1与2之间MMP-3mRNA和蛋白的表达没有显著差异（P均〉0．05）。结论MMP-3的表达增加可能参与腰椎间盘退变的进程。     

MMP-1、MMP-9 mRNA在创伤性骨关节炎软骨中的表达

目的 研究兔前交叉韧带横断术(ACLT)创伤性骨关节炎(OA)动态模型软骨中MMP-1、MMP-9 mRNA的表达,探讨MMP-1、MMP-9在OA软骨退变中的作用.方法 30只新西兰兔随机分为对照组(10只)、ACLT组(20只),ACLT组行右膝ACLT,对照组行关节囊切开缝合术,ACLT组于术后4、8 w各处死10只,对照组术后4 w处死.解剖显微镜观察股骨内髁软骨形态学变化,逆转录聚合酶链反应(RT-PCR)检测股骨内髁软骨MMP-1、MMP-9 mRNA的表达.结果 形态学示ACLT组软骨退变重于对照组(P<0.05),且ACLT 8 w组重于4 w组(P<0.05);RT-PCR示ACLT组MMP-1、MMP-9 mRNA表达量均高于对照组(P<0.01),且ACLT 8 w组均高于4 w组(P<0.01).结论 创伤性OA软骨退变过程中伴随着MMP-1、MMP-9 mRNA表达的上调,软骨中MMP-1、MMP-9 mRNA的表达一定程度上反映了OA软骨的退变程度.     

胆管癌组织中MMP-9的表达及其意义

目的　探讨基质金属蛋白酶 9(matrixmetalloproteinase 9,MMP 9)在胆管癌发展中的作用及与胆管癌浸润、转移和预后的关系。方法　应用免疫组织化学法 (S P法 )对 5 2例经手术和病理证实的胆管癌及 10例经手术切除的正常胆管壁标本进行MMP 9蛋白检测。结果　 (1)MMP 9表达在胆管癌组织、癌旁组织及正常胆管上皮组织阳性率分别为 84 6 % (4 4 /5 2 )、2 2 6 % (7/31)和 0 %(0 /10 ) ,有显著性差异 (P <0 0 1)。 (2 )在 5 2例胆管癌组织中 ,MMP 9表达分别与肿瘤的病理分级、TNM分期、浸润和转移及手术方式有关 (P <0 0 5 ) ,而与性别、年龄、肿瘤部位及大小无关 (P >0 0 5 )。 (3)MMP 9表达阳性患者一年生存率明显低于阴性者 (P <0 0 1)。结论　MMP 9表达与胆管癌发展、浸润和转移密切相关 ,检测MMP 9的表达有助于对胆管癌转移潜能和预后的判断。     

基质金属蛋白酶-3在突出椎间盘中的表达及其意义

目的：检测椎间盘突出症的椎间盘中是否有基质金属蛋白酶－３（ＭＭＰ３）的表达,以便进一步了解椎间盘突出症的发病机制。方法：运用免疫组织化学抗生物素蛋白－生物素－过氧化物酶复合体法,通过抗ＭＭＰ３的单克隆抗体,对７８例椎间盘突出症和１４例非椎间盘突出症的椎间盘标本进行染色。结果：椎间盘突出症中的ＭＭＰ３比非椎间盘突出的多,差异非常显著。椎间盘突出症的临床分型：脱出型及游离型的ＭＭＰ３比凸出型的多,其差     

轻度慢性乙型肝炎患者肝组织中MMP-2和TIMP-2的表达及其意义

目的 探讨轻度慢性乙型肝炎(CHB)患者肝组织中的基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶抑制剂-2(TIMP-2)的表达及临床意义.方法 选取2006年12月至2011年12月温州医学院附属第二医院感染内科收治入院的慢性HBV感染者68例为研究对象,将其分为轻度慢性乙型肝炎(CHB)组(35例)和慢性HBV携带组(33例).采集患者血清,行HBV血清学标志物、HBVDNA、肝纤维化血清学指标检测及肝穿刺活检,光镜下观察肝组织.采用免疫组织化学染色法检测MMP-2和TIMP-2的表达,并进行阳性表达评分及肝组织纤维化分级.用SPSS 17.0软件进行统计学分析.结果 轻度CHB组和慢性HBV携带者组血清肝纤维化指标透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型胶原(PC Ⅲ)和Ⅳ型胶原(CⅣ)的差异无统计学意义(t=1.35,1.65,1.88和1.89,P＞0.05).轻度CHB组肝组织中MMP-2和TIMP-2评分分别为(4.42±1 37)和(3.89±1.12)分,慢性HBV携带组分别为(3.61 ±1.23)和(3.31±1.07)分,差异有统计学意义(t=2.56和2.18,P＜0.05).CHB组的MMP-2/TIMP-2比值为1.15±0.17,而慢性HBV携带组为1.08-±0.11,两组比较差异有统计学意义(t=2.04,P＜0.05).MMP-2和TIMP-2评分与纤维化分级的相关系数分别为0.372(P =0.002)和0.439(P =0.000).结论 轻度CHB患者的肝组织中MMP-2和TIMP-2表达增加,且与纤维化分级具有相关性,可用于评估患者肝纤维化的程度.     

MMP-2、MMP-9、TIMP-1在血管成形术后再狭窄中的表达及其意义的实验研究

目的观察PTA后MMP-2、MMP-9和TIMP-1在血管壁各层随时间的演变规律,探讨其在血管再狭窄过程中的表达及意义。方法48只大鼠制作成颈动脉再狭窄动物模型,选取30只内膜增生满意的标本,分别代表动脉损伤后1、3、7、14、28、42天6个观察时间点,对胶原纤维进行Masson染色。MMP-2、TIMP-1、PCNA进行免疫组织化学染色,MMP-9进行免疫组织化学和原位杂交两种染色。分析它们的表达与内膜增生和血管重塑的关系。结果正常血管不表达MMP-9mRNA及蛋白,损伤后第3天中膜、外膜mRNA表达达高峰,第7天内膜表达达高峰。MMP-9蛋白第7天内膜表达达高峰,且阳性细胞率高于中膜和外膜。第14、28天,血管壁各层表达逐渐下降至基线水平,内膜的阳性细胞主要集中在新生内膜靠近管腔的一侧。内膜MMP-2表达高峰出现晚至第14天,且近内弹力板处MMP-2也有明显的表达。正常血管壁不表达TIMP-1,损伤后第3天,中膜和外膜表达达高峰。第7天,新生内膜表达达高峰,中膜和外膜仍有较高水平表达。结论MMP-9、MMP-2、TIMP-1参与再狭窄,内膜MMP-9表达与早期增殖的细胞向内膜迁移形成新生内膜有关。MMP-2表达与晚期内膜形成、内膜重塑有关。TIMP-1的表达对内膜增生和重塑没有直接作用,其表达升高是机体为适应MMPs升高做出的代偿反应,在维持自身平衡中起作用。     

MMP-1和MMP-2在肝纤维化组织中的表达和意义

目的:探讨MMP-1和MMP-2在肝纤维化组织中的作用及其机制。方法:应用免疫组化法并用图像分析技术定量检测28例手术切除的肝纤维化组织标本中MMP-1和MMP-2的表达。结果:正常肝组织与肝纤维化组织MMP-1表达无显著性差异(P>0.05),而MMP-2的表达在肝纤维化组织中明显高于正常肝组织(P<0.01)。结论:MMP-1和MMP-2可能在肝纤维化的发生和发展中有重要作用。     

The Biochemical Response of Rabbit Articular Cartilage Matrix to an Induced Talcum Synovitis

Transient synovitis is a commonly occurring affliction in the hips of young children. The results of an experimental model of this condition produced in the immature rabbit's hip showed that there is a significant response in the articular cartilage. Thus, the cartilage rapidly thickens, becomes more hydrated and reveals an initial decrease in glycosaminoglycan concentration. Three weeks following the induction of synovitis, the concentrations of water, glycosaminoglycan and collagen are similar to the control side. The increase of articular cartilage mass is due, not only to an increased hydration, but also to increased matrix production under the stimulus of the synovitis. A similar response by the immature cartilage might be expected following a transient synovitis in a child's hip.     

同种异体软骨细胞移植术后关节软骨蛋白多糖的测定

目的 应用Pluronic F-127负载同种异体软骨细胞移植修复兔全厚关节软骨损伤,对于新生的修复组织进行基质蛋白多糖含量测定,以探讨此方法修复全厚关节软骨损伤的可行性.方法 取3个月龄新西兰大白兔关节软骨细胞体外培养扩增,与20%Plurortic F-127凝胶混合.选27只健康同种成年大白兔,人为造成双侧膝关节软骨缺损.实验组软骨缺损处植入培养的软骨细胞/Pluronic F-127混合物,对照组缺损处单纯注入Pluronic F-127凝胶和空白对照.然后,对修复组织进行大体观察及蛋白多糖含量测定.结果 移植的软骨细胞-载体复合物中的软骨细胞能良好地生长,12周时再生组织与周围正常软骨组织外观相似,界限模糊.实验组与对照组各时期蛋白多糖含量均有非常显著性差异,实验组不同时期的蛋白多糖含量之间均有显著性差异,实验组12周时蛋白多糖含量与正常软骨组织无显著性差异.结论 Pluronic F-127负载同种异体软骨细胞移植是治疗关节软骨缺损的有效方法.     

Development of Partial-thickness Articular Cartilage Injury in a Rabbit Model

In humans, partial-thickness cartilage lesions frequently result in premature osteoarthritis. While rabbits often are used as a model for partial-thickness cartilage lesions, the natural course of cartilage surrounding such a lesion is largely unknown. We developed a rabbit model of a chronic partial-thickness cartilage defect and asked whether these defects led to (1) deterioration of surrounding cartilage macroscopically and microscopically (increased Mankin score) and (2) disturbances in proteoglycan metabolism. In 55 rabbits, we created a 4-mm-diameter partial-thickness cartilage defect on one medial femoral condyle. The surrounding cartilage was characterized during the course of 26 weeks. Contralateral knees were sham-operated. In experimental knees, we found cartilage softening and fibrillation at 13 and 26 weeks. High Mankin scores observed at 1 week were partially restored at 13 weeks but worsened later and were most pronounced at 26 weeks. Mankin scores in the experimental groups were worse at 1 and 26 weeks when compared with the sham groups. Mankin scores at 26 weeks improved compared with 1 week in the sham groups. Disturbances in proteoglycan metabolism were less evident. In this rabbit model, a partial-thickness cartilage lesion resulted in early markers of degenerative changes resembling the human situation. Each author certifies that he has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.     

Aggrecan and Cartilage Oligomeric Matrix Protein in Serum and Synovial Fluid of Patients with Knee Osteoarthritis

Aggrecan and cartilage oligomeric matrix protein (COMP) which are important degradation products of articular cartilage may be promising diagnostic markers in serum and/or synovial fluid for diagnosis of knee osteoarthritis (OA). Our objective was to measure serum and synovial fluid levels of aggrecan and COMP in patients with OA of the knee joint to find out if they could be of diagnostic value in OA and if their levels correlate with the clinical and radiological manifestations of the disease. Sixty-six patients suffering from primary knee OA with effusion (26 males and 40 females) were studied. Twenty individuals (six males and 14 females) with recent traumatic knee effusion matched for age and sex were chosen to serve as a control group. All subjects had thorough clinical and radiological (X-ray and MRI) evaluation. Aggrecan and COMP in serum and synovial fluid were measured by ELISA. Serum and synovial fluid aggrecan and COMP levels were significantly higher than the control. Serum and synovial fluid aggrecan and COMP levels were positively correlated with age, body mass index, disease duration, plain X-ray and MRI scores. In OA, serum and synovial fluid aggrecan and COMP levels are elevated and represent useful markers in the diagnosis. Moreover, these elevated levels positively correlated with radiological joint damage but not with clinical disease parameters. These markers have the potential to be used for monitoring articular cartilage destruction and response to different therapeutic modalities.     

Nucleic Acids in Human Normal and Osteoarthritic Articular Cartilage

During operations on joints of patients with osteoarthritis, specimens of severely degenerated cartilage of the femoral head were removed and cartilage from knee joints taken at meniscectomy was used as control material. DNA and RNA concentrations were reduced in advanced osteoarthritis, while the synthesis of DNA and RNA was increased in relation to the number of cells in the tissue. The result showed that in advanced osteoarthritis the remaining chondrocytes are metabolically very active.     

Demineralized Dentin Matrix Acts as a Scaffold for Repair of Articular Cartilage Defects

Articular cartilage repair remains a major obstacle in tissue engineering. In the present study, we investigated the potential for demineralized dentin matrix (DDM; organic material derived from dentin) obtained from extracted teeth to be used as bone graft material. To evaluate the extent to which DDM induces osteochondral regeneration, we implanted DDM from bovine teeth in rabbit knees with full-thickness articular cartilage defects. Thirty-three 13-week-old male rabbits weighing 2.5–3.0 kg were randomly assigned to a control group (n = 11) and two experimental groups (n = 11 for each group). The knees were divided into three groups according to the subsequent treatment: in group I (n = 22), the control group, the defect was left untreated; and in groups II (n = 22) and III (n = 22), 50 and 100 mg of DDM, respectively, was implanted. The rabbits were killed 1, 3, 6, or 9 weeks after the surgical procedure, and the knees were collected. The harvested tissues were examined radiographically and histologically. The 100-mg DDM group (group III) had significantly more new bone forming inside the defect (as measured using the BV/TV value) compared with the other two groups as early as at week 3 postoperatively, but thereafter, the difference gradually decreased. Cartilage repair in the surface region remained significantly better in group III because hyaline-like cartilage appeared in the peripheral area of the defect at week 6 and the surface was covered with hyaline-like cartilage with a thickness similar to that of normal cartilage at week 9. In conclusion, the results of this study suggest that DDM acts as a scaffold for osteochondral regeneration, yielding active new bone formation early in the postoperative period. Thus, DDM may represent an effective bone implant material.     

同种异体软骨细胞移植修复兔膝关节软骨缺损的免疫反应

目的：探讨同种异体软骨细胞移植修复关节软骨缺损的免疫学变化。方法：将兔分成软骨细胞移植组及骨基质明胶移植组，用免疫学及组织学方法，研究其免疫反应。结果：软骨细胞移植组术后检到淋巴细胞增殖，植入物局部见到淋巴细胞浸润。结论：同种异体软骨细胞移植存在免疫反应。     

Combined Injury to the ACL and Lateral Meniscus Alters the Geometry of Articular Cartilage and Meniscus Soon After Initial Trauma

Combined injury to the anterior cruciate ligament (ACL) and meniscus is associated with earlier onset and increased rates of post-traumatic osteoarthritis compared with isolated ACL injury. However, little is known about the initial changes in joint structure associated with these different types of trauma. We hypothesized that trauma to the ACL and lateral meniscus has an immediate effect on morphometry of the articular cartilage and meniscus about the entire tibial plateau that is more pronounced than an ACL tear without meniscus injury. Subjects underwent magnetic resonance imaging scanning soon after injury and prior to surgery. Those that suffered injury to the ACL and lateral meniscus underwent changes in the lateral compartment (increases in the posterior–inferior directed slopes of the articular cartilage surface, and the wedge angle of the posterior horn of the meniscus) and medial compartment (the cartilage-to-bone height decreased in the region located under the posterior horn of the meniscus, and the thickness of cartilage increased and decreased in the mid and posterior regions of the plateau, respectively). Subjects that suffered an isolated ACL tear did not undergo the same magnitude of change to these articular structures. A majority of the changes in morphometry occurred in the lateral compartment of the knee; however, change in the medial compartment of the knee with a normal appearing meniscus also occurred. Statement of clinical significance: Knee injuries that involve combined trauma to the ACL and meniscus directly affect both compartments of the knee, even if the meniscus and articular cartilage appears normal upon arthroscopic examination. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:759-767, 2020