Matrilin-3 in human articular cartilage: increased expression in osteoarthritis

OBJECTIVE: Matrilin-3 is a member of the recently described matrilin family of extracellular matrix proteins containing von Willebrand factor A-like domains. The matrilin-3 subunit can form homo-tetramers as well as hetero-oligomers together with subunits of matrilin-1 (cartilage matrix protein). It has a restricted tissue distribution and is strongly expressed in growing skeletal tissues. Detailed information on expression and distribution of extracellular matrix proteins is important to understand cartilage function in health and in disease like osteoarthritis (OA). METHODS: Normal and osteoarthritic cartilage were systematically analysed for matrilin-3 expression, using immunohistochemistry, Western blot analysis, in situ hybridization, and quantitative PCR. RESULTS: Our results indicate that matrilin-3 is a mandatory component of mature articular cartilage with its expression being restricted to chondrocytes from the tangential zone and the upper middle cartilage zone. Osteoarthritic cartilage samples with only moderate morphological osteoarthritic degenerations have elevated levels of matrilin-3 mRNA. In parallel, we found an increased deposition of matrilin-3 protein in the cartilage matrix. Matrilin-3 staining was diffusely distributed in the cartilage matrix, with no cellular staining being detectable. In cartilage samples with minor osteoarthritic lesions, matrilin-3 deposition was restricted to the middle zone and to the upper deep zone. A strong correlation was found between enhanced matrilin-3 gene and protein expression and the extent of tissue damage. Sections with severe osteoarthritic degeneration showed the highest amount of matrilin-3 mRNA, strong signals in in situ hybridization, and prominent protein deposition in the middle and deep cartilage zone. CONCLUSION: We conclude that matrilin-3 is an integral component of human articular cartilage matrix and that the enhanced expression of matrilin-3 in OA may be a cellular response to the modified microenvironment in the disease.     

Pericellular matrilins regulate activation of chondrocytes by cyclic load-induced matrix deformation.

Pericellular matrix is at the ideal location to be involved in transmitting mechanical signals from the microenvironment to a cell. We found that changes of the content of matrilins that link various pericellular molecules surrounding chondrocytes affect mechanical stimulation of chondrocyte proliferation and gene expression. Thus, pericellular matrilins may play a role in chondrocyte mechanotransduction. INTRODUCTION: Chondrocytes reside in a capsule of pericellular matrix (chondron), which has been hypothesized to play a critical role in transducing mechanical signals to the cell. In this study, we test the hypothesis that the levels of matrilin (MATN)-1 and -3, major components of the chondrocyte pericellular matrix network, regulate activation of chondrocyte proliferation and differentiation by cyclic load-induced matrix deformation. MATERIALS AND METHODS: Functional matrilins were decreased by expressing a dominant negative mini-MATN in primary chondrocytes or by using MATN1-null chondrocytes. The abundance of matrilins was also increased by expressing a wildtype MATN1 or MATN3 in chondrocytes. Chondrocytes were cultured in a 3D sponge subjected to cyclic deformation at 1 Hz. Chondrocyte gene expression was quantified by real-time RT-PCR and by Western blot analysis. Matrilin pericellular matrix assembly was examined by immunocytochemistry. RESULTS: Elimination of functional matrilins from pericellular matrix abrogated mechanical activation of Indian hedgehog signaling and abolished mechanical stimulation of chondrocyte proliferation and differentiation. Excessive or reduced matrilin content decreased mechanical response of chondrocytes. CONCLUSIONS: Normal content of matrilins is essential to optimal activation of chondrocytes by mechanical signals. Our data suggest that the sensitivity of chondrocytes to the changes in the microenvironment can be adjusted by altering the content of matrilins in pericellular matrix. This finding supports a critical role of pericellular matrix in chondrocyte mechano-transduction and has important implications in cartilage tissue engineering and mechanical adaptation.     

O-linked glycosylation and functional incompatibility of porcine von Willebrand factor for human platelet GPIb receptors

BACKGROUND: Xenograft rejection is associated with vascular inflammation, thrombocytopenia and the accelerated consumption of coagulation factors. Primary biological incompatibilities of the xenograft in the regulation of clotting appear to amplify pathological processes associated with rejection. The functional incompatibility of porcine von Willebrand factor (vWF) expressed within the xenograft vasculature may heighten interactions with the primate platelet receptor GPIb, hence augmenting formation of platelet microthrombi and vascular injury. Here, we address the functional impact of O-linked glycosylation of the vWF A1 domain on primate platelet activation. METHODS: Recombinant human or porcine vWF A1-domains were transiently over-expressed in COS-7 cells as FLAG-tagged fusion protein, linked to plasma membranes via GPI anchors. O-linked glycosylation was blocked by the addition of phenyl-alpha-GalNAc2 to cultures. Expressed vWF-A1 domains were characterized utilizing cytofluometric- and Western blot analyses. RESULTS: Cytofluometric analysis confirmed equivalent levels of human and porcine vWF A1-domain expression irrespective of the levels of O-linked glycosylation. Differential glycosylation patterns of vWF-A1 under these conditions were confirmed by Western blot analyses. Native porcine vWF A1-domains had enhanced human platelet activation potential when compared with human recombinant vWF A1. However, the loss of O-linked glycosylation abolished differences in aggregatory responses between human and porcine vWF A1 domains. CONCLUSIONS: Various degrees of O-linked glycosylation of vWF-A1-domains modulate levels of functional interaction with platelet receptor GPIb and consequent platelet aggregation responses in vitro. These data may have implications for outcomes of xenotransplantation. We speculate that alterations in glycosylation of vWF and other adhesion proteins associated with the targeting of the alpha1,3-Gal-epitope in mutant swine may have salutatory effects on the primate platelet activation observed in these xenografts.     

Expression of mutant cartilage oligomeric matrix protein in human chondrocytes induces the pseudoachondroplasia phenotype.

Over 70 mutations in the cartilage oligomeric matrix protein (COMP), a large extracellular pentameric glycoprotein synthesized by chondrocytes, have been identified as causing two skeletal dysplasias: multiple epiphyseal dysplasia (MED/EDM1), and a dwarfing condition, pseudoachondroplasia (PSACH). These mutations induce misfolding of intracellular COMP, resulting in retention of the protein in the rough endoplasmic reticulum (rER) of chondrocytes. This accumulation of COMP in the rER creates the phenotypic enlarged rER cisternae in the cells, which is believed to compromise chondrocyte function and eventually cause cell death. To study the molecular mechanisms involved with the disease, we sought to develop an in vitro model that recapitulates the PSACH phenotype. Normal human chondrocytes were transfected with wildtype (wt-) COMP or with mutant COMP (D469del; mt-) recombinant adenoviruses and grown in a nonattachment redifferentiating culture system that provides an environment allowing formation of a differentiated chondrocyte nodule. Visualization of normal cells expressing COMP suggested the hallmarks of the PSACH phenotype. Mutant COMP expressed in normal cells was retained in enlarged rER cisternae, which also retained IX collagen (COL9) and matrilin-3 (MATN3). Although these proteins were secreted normally into the ECM of the wt-COMP nodules, reduced secretion of these proteins was observed in nodules composed of cells transfected with mt-COMP. The findings complement those found in chondrocytes from PSACH patient growth plates. This new model system allows for production of PSACH chondrocyte pathology in normal costochondral chondrocytes and can be used for future mechanistic and potential gene therapy studies.     

Extracellular matrix in disc degeneration

The extracellular matrix of the intervertebral disc structures contains many molecules also found in cartilage. The extremely polyanionic proteoglycans play a central role, particularly in the nucleus, by creating an osmotic environment leading to retention of water and ensuing resistance to deformation-important for the resilience of the tissue. Another major structural entity particularly important in the anulus is the network of collagen fibers; fibril-forming collagen 1 is a major constituent. The collagen fibrils in the anulus are largely oriented in sheets around the nucleus. A number of molecules present in the matrix regulate and direct the collagen fibril assembly by interacting with the collagen molecule and also the formed fibril. Several of these molecules bind by one domain to the collagen fiber and present another functional domain to interact either with other fibers or with other matrix constituents. In this manner the collagen fibers are cross-linked into a network that provides tensile strength and distributes load over large parts of the anulus. Diminished function in these cross-bridging molecules will lead to loss of mechanical properties of the collagen network and result in an impaired ability of the anulus to resist forces delivered by compression of the disc and particularly the nucleus. A different network abundant in the disc and in other load-bearing tissues is based on the beaded filaments of collagen 6. The basic building block is a tetramer of two pairs of antiparallel collagen-6 molecules arranged such that two N-terminal ends of collagen 6 are exposed at either end of the unit. Further assembly occurs both by end-to-end and side-to-side associations. This process is catalyzed by both biglycan and decorin, where the combined effect of direct binding of the core protein to the collagen-6 N-terminal globular domain and the presence of the glycosaminoglycan side chain is essential. These ligands are bound at the same site in complexes extracted from the tissue and then also have one bound molecule of matrilin-1, 2, or 3, in turn bound to a collagen fiber, a procollagen molecule, or an aggrecan. Interactions at the cell surface provide signals to the cells with regard to the conditions of the matrix. Such interactions include binding by matrix components to various receptors at the cell surface. Remodeling of the matrix takes place in response to various factors. An early event in disease is degradation of aggrecan by the members of the ADAMTS (a disintegrin-like and metalloprotease with thrombospondin motifs) family and degradation of molecules important in maintaining the collagen network.     

Alternative splicing of exon 12 of the COL2A1 gene interrupts the triple helix of type-II collagen in the kniest form of spondyloepiphyseal dysplasia

An autosomal dominant mutation in the COL2A1 gene was identified in a child with the Kniest form of spondyloepiphyseal dysplasia. A C to T transition at nucleotide 35 of exon 12 changed the codon GCG for alanine 102 of the triple helical domain of α1 (II) chains of type-II collagen to GTG for valine. The transition also introduced a GT dinucleotide into exon 12. Analysis of cDNA prepared from Kniest cartilage showed that in vivo the transition resulted in an alternatively spliced mRNA that lacked the 21 3′ nucleotides from exon 12. The cartilage cDNA contained approximately equal amounts of normal cDNA and shortened mutant cDNA. The deletion of 21 nucleotides from the mutant cDNA maintained the translational reading frame but resulted in the loss of alanine 102 to lysine 108, which interrupted the repetitive glycine-X-Y triplet sequence required for formation of the triple helix. Type-II collagen molecules containing one or more mutant chains were expected, therefore, to contain interrupted triple helices with a short amino-terminal helical domain A and a large carboxy-terminal helical domain B. Kniest cartilage contained a reduced amount of pepsin-solubilized type-II collagen that consisted of overmodified α1 (II) chains. Peptide mapping showed that the overmodifications extended to the carboxy terminus of the α1(II) chains. Pepsin digestion also yielded shortened α1 (II) chains corresponding to helical domain B, Kniest chondrocytes cultured in alginate beads produced type-II collagen that was not stably incorporated into the pericellular matrix. This study highlights the importance of dominant negative mutations of COL2A1 in producing Kniest dysplasia.     

Urokinase-type plasminogen activator (uPA) and its inhibitor--new prognostic factors in oral squamous cell carcinoma

Several cell biological studies have shown that the invasiveness of different malignant tumors (breast, renal, prostate, gastric, ovarian cancers) depends at least in part on the urokinase type plasminogen activator (uPA) and its inhibitor PAI1. uPA converts plasminogen into plasmin. Plasmin degrades tumor matrix components and starts invasion and metastasis. Our target was to see the possible prognostic relevance of the tumor-associated proteolytic factors and to compare with tumor size, nodal status and grading. Our results suggest that the invasive and metastatic potential of squamous cell carcinoma is correlated with overexpression of uPA and PAI1.     

Osteochondral autograft for medial femoral condyle chondral lesions in a patient with multiple epiphyseal dysplasia: long-term result

Multiple epiphyseal dysplasia (MED) is a form of osteochondrodysplasia characterized by abnormal epiphyseal growth and assumed to be a clinical condition of extracellular matrix abnormality [1]. Osteoarthritis and chondral lesions, for example osteochondritis dissecans (OCD), are among the clinical expressions of MED [2, 3]. It is possible for osteoarthritic changes of the knee to develop easily even in young patients with MED [4]. Total knee arthroplasty (TKA) and correction osteotomy have been performed for severe deformity and destruction of the knee in MED patient [4, 5].     

Increased platelet aggregation and production of platelet-derived microparticles after surgery for upper gastrointestinal malignancy

BACKGROUND: Since platelet function is known to play a major role in arterial thrombosis, we investigated postsurgery alterations in platelet function that might predispose patients with upper gastrointestinal malignancy to postoperative thrombotic complications. SUBJECTS AND METHODS: Shear-induced platelet aggregation (SIPA) in platelet-rich plasma was measured in 23 patients who elected to undergo abdominal surgery. Measurement was done by cone-plate viscometer under low shear stress (12 dyn/cm(2)), a physiological condition, and under high shear stress (108 dyn/cm(2)), a pathological condition that simulates in vivo conditions such as those in stenotic arteries. Platelet microparticle (PMP) formation was analyzed by flow cytometry. Plasma von Willebrand factor (vWF) was also measured. RESULTS: SIPA under high shear stress was significantly enhanced from 44.0 +/- 13.4% preoperatively to 69.5 +/- 15.8% on postoperative day (POD) 1, and it returned to preoperative levels on POD 14. PMP formation under high shear stress was enhanced before surgery (140.8 +/- 38.7%) compared to that under a static condition, and the enhancement was further augmented on POD 1 (219.1 +/- 49.3%). The enhancement of SIPA and PMP formation had no association with disease stage. vWF levels increased significantly on POD 1. Exogenous vWF augmented SIPA and PMP formation under high shear stress, and this augmentation was inhibited by anti-vWF antibody. CONCLUSIONS: Because PMPs are highly procoagulant, increased SIPA and PMP formation induced by surgical intervention possibly contribute to thrombotic complications. Blockage of platelet interaction with vWF may prevent arterial thrombus formation perioperatively.     

A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix

Amelogenins, the principal proteins in the developing enamel microenvironment, self-assemble into supramolecular structures to govern the remodeling of a proteinaceous organic matrix into longitudinally ordered hydroxyapatite nanocrystal arrays. Extensive in vitro studies using purified native or recombinant proteins have revealed the potential of N-terminal amelogenin on protein self-assembly and its ability to guide the mineral deposition. We have previously identified a 14-aa domain (P2) of N-terminal amelogenin that can self-assemble into amyloid-like fibrils in vitro. Here, we investigated how this domain affects the ability of amelogenin self-assembling and stability of enamel matrix protein scaffolding in an in vivo animal model. Mice harboring mutant amelogenin lacking P2 domain had a hypoplastic, hypomineralized, and aprismatic enamel. In vitro, the mutant recombinant amelogenin without P2 had a reduced tendency to self-assemble and was prone to accelerated hydrolysis by MMP20, the prevailing metalloproteinase in early developing enamel matrix. A reduced amount of amelogenins and a lack of elongated fibrous assemblies in the development enamel matrix of mutant mice were evident compared with that in the wild-type mouse enamel matrix. Our study is the first to demonstrate that a subdomain (P2) at the N-terminus of amelogenin controls amelogenin's assembly into a transient protein scaffold that resists rapid proteolysis during enamel development in an animal model. Understanding the building blocks of fibrous scaffold that guides the longitudinal growth of hydroxyapatites in enamel matrix sheds light on protein-mediated enamel bioengineering. © 2021 American Society for Bone and Mineral Research (ASBMR).     

青少年特发性脊柱侧凸患者血浆matrilin-1蛋白水平及其临床意义

目的 探讨青少年特发性脊柱侧凸(AIS)患者外周血中matrilin-1蛋白水平的变化及其在AIS发病机制中的作用.方法 将2006年6月至2007年3月诊治的25例AIS患者作为AIS组,25名性别、年龄相匹配的健康体检青少年作为对照组.所有入选对象符合以下标准:无骨骼疾病、代谢疾病、生长发育异常;无影响骨代谢的系统疾病及其他情况;近期未服用激素;无先天性心脏病手术史.AIS组记录末次随访或术前最大Cobb角、侧凸弯型,并分为进展型及非进展型两组.进展型侧凸(侧凸进展成为严重脊柱侧凸)定义为骨骼发育未成熟时,Cobb角＞40°或骨骼发育成熟时,Cobb角＞50°.采用PCR-RFLP基因分型方法 对所有对象进行基因分型,运用酶联免疫吸附(ELISA)法检测AIS组与对照组外周血浆中matrilin-1蛋白浓度并比较其差异,并对不同基因型之间matrilin-1蛋白的表达进行比较.分析血浆matrilin-1蛋白浓度与脊柱侧凸进展的关系.结果 AIS组血浆matrilin-1蛋白浓度显著低于对照组(P=0.002).AIS组及对照组的基因型GG个体血浆matrilin-1蛋白浓度均低于基因型AA或AG个体,而对于相同基因型的个体AIS组血浆matrilin-1蛋白水平更低.进展型AIS患者血浆matrilin-1蛋白水平明显较非进展型AIS患者低.结论 AIS患者外周血matrilin-1蛋白水平与脊柱侧凸的进展相关.对外周血matrilin-1蛋白浓度的检测,有助于AIS的早期筛查及诊断,可作为预测脊柱侧凸进展的一个独立指标.     

Effects of Celecoxib on High‐Sensitivity C‐Reactive Protein in Chronic Peritoneal Dialysis Patients

To evaluate the effects of celecoxib, a cyclooxygenase‐2 inhibitor, on the level of high‐sensitivity C‐reactive protein (hs‐CRP), D‐dimer, von Willebrand factor (vWF) and troponin‐T, 46 chronic peritoneal dialysis (CPD) patients with hs‐CRP equal or greater than 0.25 mg/dL were randomized to the treatment group who took 200 mg of celecoxib daily for 4 weeks or to the control group who did not take the medication. The levels of hs‐CRP, albumin, D‐dimer, vWF and troponin‐T were measured at baseline and at 4 weeks of the study. Baseline values of all the parameters were not significantly different between the two groups. In the control group, the levels of hs‐CRP, albumin, D‐dimer, vWF and troponin‐T did not change. In the treatment group, administration of celecoxib for 4 weeks significantly reduced hs‐CRP from median 0.77 (range 0.25–7.08) to 0.39 mg/dL (range 0.11–5.22, p < 0.05). The levels of albumin, D‐dimer, vWF and troponin‐T levels were not affected by the administration of celecoxib. These results showed that celecoxib had an antiinflammatory effect in usual dosage in CPD patients.     

膜1型基质金属蛋白酶在骨代谢作用中的研究进展

基质金属蛋白酶是一类锌依赖性内肽酶,可降解大多数细胞外基质。膜1型基质金属蛋白酶(membrane type-1 matrix metalloproteinase,MT1-MMP或MMP14)属于基质金属蛋白酶家族,是唯一一种能够直接促进细胞向3D胶原蛋白基质入侵的胶原酶。骨细胞胞外基质在骨形成和骨吸收过程中发挥重要作用,MT1-MMP通过影响胞外基质引起骨骼相关的病理、生理变化。本文拟就近年MT1-MMP在骨代谢作用中的研究进展进行综述,旨在为MT1-MMP在骨代谢疾病的药理干预、骨生物工程中的应用提供新思路。     

Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podocyte adhesion, architecture, and survival

Alterations in the cellular architecture, adhesion, and/or loss of glomerular podocytes are causal factors in the development of proteinuria and the progression to end-stage renal failure. With the use of an inducible podocyte differentiation system, it was found that the cellular levels of PINCH-1, integrin linked kinase (ILK), and alpha-parvin, cytoplasmic components of cell-extracellular matrix adhesions, were significantly increased during podocyte differentiation. Concomitantly, an increased amount of the PINCH-1-ILK-alpha-parvin complex was detected in the differentiated, foot process-containing podocytes. Overexpression of the PINCH-1-binding ankyrin repeat domain of ILK but not that of a PINCH-1-binding defective mutant form of the ankyrin domain effectively inhibited the formation of the PINCH-1-ILK-alpha-parvin complex. Disruption of the PINCH-1-ILK-alpha-parvin complex significantly reduced the podocyte-matrix adhesion and foot process formation. Furthermore, a marked increase of apoptosis in the podocytes in which the assembly of the PINCH-1-ILK-alpha-parvin complex was compromised was detected. Inhibition of ILK with a small compound inhibitor also altered podocyte cytoskeleton and increased apoptosis. Finally, it is shown that alpha-parvin is phosphorylated in podocytes. Mutations at the alpha-parvin N-terminal proline-directed serine phosphorylation sites reduced its complex formation with ILK and resulted in defects in podocyte adhesion, architecture, and survival. These results provide important evidence for a crucial role of the PINCH-1-ILK-alpha-parvin complex in the control of podocyte adhesion, morphology, and survival.     

Cartilage degradation independent of MMP/aggrecanases

OBJECTIVE: To identify and characterize a cartilage degradation mechanism that is independent of the proteolytic cleavages by matrix metalloproteinases (MMPs) and aggrecanases. METHODS: The sensitivity of glycosaminoglycan (GAG) release and collagen release to an MMP/aggrecanase inhibitor, AG3340, was compared using a bovine nasal cartilage explant culture. The release of matrix proteins and hyaluronan (HA) from the culture was analyzed by immunoblotting and radioimmunoassay, respectively. Induction of HA-degrading activity by retinoic acid was examined using the cartilage explant culture and a primary culture of chondrocytes. Degradation of the matrix components of cartilage was also characterized in vivo using an acute arthritis model induced by an intra-articular injection of interleukin 1alpha (IL-1alpha). RESULTS: AG3340 did not effectively inhibit GAG release at a concentration of more than 10muM, while 10nM of the inhibitor completely suppressed collagen degradation. Retinoic acid induced the release of the aggrecan G1 domain, link protein and HA into the culture medium, and the release of these molecules was not completely inhibited by 10muM of AG3340. The molecules were released as ternary complexes. Retinoic acid induced HA degradation in the explant culture and hyaluronidase activity in the primary culture of chondrocytes. The release of the G1 domain of aggrecan and link protein into the synovial fluid was also observed in the IL-1alpha-induced acute arthritis model. CONCLUSION: A novel mechanism by chondrocyte-derived hyaluronidase(s) is involved in the release of the matrix components from cartilage, and the hyaluronidase(s) and MMPs/aggrecanases act in a coordinated manner in cartilage degradation.     

TGF-β1/Smad3信号转导通路与创伤后瘢痕形成

目的对近年TGF-β1/Smad3信号转导通路与创伤后瘢痕形成的相关研究作一综述。方法广泛查阅国内外近年有关TGF-β1/Smad3信号转导通路及与创伤后瘢痕形成的文献,并进行综述。结果 TGF-β1是纤维化疾病的重要影响因子,通过TGF-β1/Smad3信号通路转导产生其生物学效应。该途径受多种因子调控并在细胞及分子水平与其他信号通路串话。该途径参与创伤后早期炎性反应、创面愈合及后期病理性瘢痕的形成。在分子水平干预转导途径的各个环节,可以影响纤维化及细胞外基质沉着的进程。结论 TGF-β1/Smad3信号转导途径是影响创伤后瘢痕形成及细胞外基质沉着的重要途径。对该途径进行深入研究,可为临床促进创面的愈合及病理性瘢痕的防治奠定理论基础。     

Anticonvulsant therapy increases fentanyl requirements during anaesthesia for craniotomy

This study was designed to determine whether patients receiving chronic anticonvulsant therapy demonstrate an altered requirement for fentanyl during anaesthesia. Sixty-one patients undergoing craniotomy were studied; 20 controls (MED = 0) who had never received anticonvulsants and 41 epileptics in whom therapeutic plasma concentrations of either one (MED = 1), two (MED = 2), or three (MED = 3) different anticonvulsants were documented. During anaesthesia with 60-70 per cent N2O in O2 and 0.2 per cent isoflurane, a maintenance dose (MD) of fentanyl was administered using a continuous variable-rate IV fentanyl infusion, supplemented by intermittent 50 micrograms IV boluses. In order to define the minimal dosage of fentanyl required, the MD was titrated according to increases or decreases in the heart rate and/or mean arterial pressure exceeding 15 per cent of baseline ward values. A progressively higher fentanyl MD was required in the epileptic patients (MED = 1-4.3 +/- 0.5 microgram.kg-1.hr-1; MED = 2-5.4 +/- 0.6; MED = 3-7.6 +/- 0.6) compared with the control MD (MED = 0-2.6 +/- 0.5) (P less than 0.001). These findings indicate that there appears to be a dose-effect relationship between the number of anticonvulsants received and the maintenance dose of fentanyl required during balanced anaesthesia.     

显微内窥镜椎间盘切除术的术中困难和并发症

目的 :对显微内窥镜椎间盘切除术 (microendoscopicdiscectomy ,MED)术中出现的困难和并发症进行分析 ,并探讨MED的技术特点。方法 :总结经MED治疗的 1 34例腰椎间盘突出症患者术中、术后及随访 2年以上的情况。结果 :术中出现的问题及术后并发症有 :(1 )定位错误 ;(2 )进入椎管困难 ;(3)止血困难 ;(4)损伤硬膜 ;(5)加重神经根炎症及水肿 ;(6)损伤椎间小关节 ;(7)髓核残留 ;(8)术后出血、粘连。 1 34例术后随访 2 4～ 42个月 ,症状改善率为 79 1 % ,病人满意率 93 2 %。 5例二次切开手术。结论 :MED技术优缺点兼有 ,术中出现的困难和并发症与器械因素和非器械因素有关。操作者对新技术的熟练掌握和不断改进器械性能可减少初期手术的困难和并发症     

Impact of knee joint loading on fragmentation of serum cartilage oligomeric matrix protein

The aim of the study was to examine the effect of mechanical knee joint loading on the fragmentation pattern of serum cartilage oligomeric matrix protein (COMP). Ten healthy men ran with knee orthoses that were passive or active (+30.9 N·m external flexion moments) on a treadmill (30 minute; v = 2.2 m/s). Lower-limb mechanics, serum COMP levels, and fragmentation patterns (baseline; 0, 0.5, 1, 2 hours postrunning) were analyzed. Running with active orthoses enhanced knee flexion moments, ankle dorsiflexion, and knee flexion angles (P < .05). There was an increase in serum COMP (+25%; pre: 8.9 ± 2.4 U/l; post: 10.7 ± 1.9 U/l, P = .001), COMP pentamer/tetramer (+88%; 1.88 ± 0.81, P = .007), trimer (+209%; 3.09 ± 2.65, P = .005), and monomer (+78%; 1.78 ± 0.85, P = .007) after running with passive orthoses and in serum COMP (+41%; pre: 8.5 ± 2.7 U/l; post: 11.3 ± 2.1 U/l, P < .001), COMP pentamer/tetramer (+57%; 1.57 ± 0.39, P = .007), trimer (+86%; 1.86 ± 0.47, P = .005), and monomer (+19%; 1.19 ± 0.34, P = .114) after running with active orthoses. Increased fragmentation might indicate COMP release from cartilage while running. Interestingly, 0.5 h up to 2 hours after running with passive orthoses, trimer (0.5 hour: 2.73 ± 3.40, P = .029; 2 hours: 2.33 ± 2.88, P = .037), and monomer (0.5 hour: 2.23 ± 2.33, P = .007; 1 hour: 2.55 ± 1.96, P = .012; 2 hours: 2.65 ± 2.50, P = .009) increased while after running with active orthoses, pentamer/tetramer (1 hour: 0.79 ± 0.28, P = .029), and trimer (1 hour: 0.63 ± 0.14, P = .005; 2 hours: 0.68 ± 0.34, P = .047) decreased. It seems that COMP degradation and clearance vary depending on joint loading characteristics.