摘要:

AbstractThe outcome of total joint arthroplasty is determined by biological events at the bone‐implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor‐alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone‐implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte‐macrophage colony‐stimulating factor and interleukin‐4. The present study examined the effects ofin vitrochallenge with polymethylmethacrylate particles on the expression of granulocyte‐macrophage colony‐stimulating factor by primary human monocytes/macrophages and the role of interleukin‐4 in regulating this expression. The polymethylmethacrylate particles caused a dose‐dependent release of granulocyte‐macrophage colony‐stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1beta and tumor necrosis factor‐alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin‐4 inhibited the expression of granulocyte‐macrophage colony‐stimulating factor, interleukin‐6, and tumor necrosis factor‐alpha at 48 hours in a dose‐dependent manner. The data presented in this study confirm the hypothesis that interleukin‐4 downregulates particle‐induced activation of macrophages, as demonstrated by the decre

ISSN:0736-0266    

DOI:10.1002/jor.1100170602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractAseptic loosening is thought to be due primarily to osteolysis induced by cytokines and prostaglandins that are produced in response to implant‐derived wear particles. Because endotoxin has many of the same effects as have been reported for wear particles, we hypothesized that adherent endotoxin may be responsible for the biological responses induced by wear particles. We demonstrated the presence of significant levels of adherent endotoxin on commonly used preparations of titanium particles as well as on titanium and titanium‐alloy implant surfaces. In contrast, supernatants obtained by centrifugation of particle suspensions contained approximately 1% as much endotoxin as did the particles. Therefore, it is erroneous to assume that particles do not contain endotoxin on the basis of data that it cannot be detected in their supernatants or filtrates. These results emphasize the importance of considering the potential role of adherent endotoxin when examining thein vitroeffects of wear particles and thein vivoperformance of orthopaedic implants. We also developed a protocol that removed more than 99.94% of the adherent endotoxin from the titanium particles without detectably affecting their size or shape. The removal of adherent endotoxin will allow comparison of the biological responses induced by particles with or without adherent endoto

ISSN:0736-0266    

DOI:10.1002/jor.1100170603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractAdaptive changes in the menisci and adjacent posterior capsule were documented within anterior cruciate ligament‐deficient knee (stifle) joints in the goat model. These physical changes in the menisci and capsule developed over time and were associated with reduction in the initial (time zero) abnormal anterior tibial translation following transection of the anterior cruciate ligament. At 50 N of applied force, the normal goat knee joint has a total anterior‐posterior translation of 0.6 ± 0.1 mm (± SEM) at 45° of flexion and 0.3 ± 0.1 mm at 90°. The translation immediately after transection (time zero) with 50 N of force was 8.2 ± 0.5 mm at 45° and 4.9 ± 0.9 mm at 90°. Within 8 months after transection and at 50 N of force, the treated knees had reduced translation values of 5.3 ± 0.6 mm at 45° of flexion and 2.9 ± 0.5 mm at 90°, or 35 (p<0.001) and 40% reductions, respectively, compared with the values at time zero. Magnetic resonance images of the ligament‐deficient stifle joints, as well as gross measurements and image analysis after dissection, consistently demonstrated increases in cross‐sectional area and volume of the menisci compared with the contralateral controls. These secondary changes were most pronounced in the posterior portion of the medial menisci, and histologic evaluation demonstrated hypercellularity with the accumulation of poorly organized collagen, reduced safranin O staining (proteoglycan matrix synthesis), a thickened capsule and capsule attachment, and increased vascularity at the menisc

ISSN:0736-0266    

DOI:10.1002/jor.1100170604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractStrengthening of the hamstrings is often recommended following injury and reconstruction of the anterior cruciate ligament. It has been suggested that hamstrings activity stabilizes the knee and reduces anterior cruciate ligament load during weight‐bearing flexion; however, the effects of hamstrings cocontraction on the kinematics and mechanics of the normal knee have not been assessed at physiological load levels. The aim of this study was to determine whether the addition of hamstrings force affects knee rotations, translations, and joint and quadriceps force during flexion with loads at physiological levels applied to the muscles and joints. Eight cadaveric knee specimens were tested with a servohydraulic mechanism capable of applying controlled dynamic loads to simulate quadriceps and hamstrings muscle forces throughout a physiological range of motion. A constant vertical load of physiologic magnitude was applied to the hip, and quadriceps force was varied to maintain equilibrium throughout flexion. Two conditions were tested: no hamstrings force and a constant hamstrings force equivalent to the vertical load. Hamstrings fore significantly reduced internal rotation (p<0.0001) and anterior translation (p<0.0001), increased quadriceps force (p<0.0001) and normal resultant force on the tibia (p<0.0001), and reversed the direction of the shear force on the tibia (p<0.0001). These results suggest that hamstrings strengthening following anterior cruciate ligament injury may benefit anterior cruciate ligament‐deficient and reconstructed knees by reducing the load in the ligament; however, they also imply that this comes at the expense of efficiency and higher patellofemoral and joint for

ISSN:0736-0266    

DOI:10.1002/jor.1100170605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe patellar tendon is the most commonly used graft source in reconstruction of the anterior cruciate ligament. The performance of a patellar tendon graft in such a reconstruction is largely related to the structural and functional differences between patellar tendons and anterior cruciate ligaments. From a genetic point of view, the structural and functional differences are ultimately decided by the differential patterns of gene expression between the two tissues. In the present study, the genetic differences between normal patellar tendons and normal anterior cruciate ligaments were explored by screening a large number of mRNA species to detect the species unique to each tissue. Of the approximately 1,000 mRNAs screened, 20 differentially expressed mRNA species were detected. Eight were unique to patellar tendons, and 12 were unique to anterior cruciate ligaments. Of these 20 unique mRNA species, 12 did not match any of the known sequences in gene databases and were probably novel genes. Transcriptional control is a major step in the genetic pathway: therefore, the variations found between patellar tendons and anterior cruciate ligaments at this level of gene expression indicate that the differences between the two tissues are likely more extensive than previously thought. These differences probably influence the survival of patellar tendon autografts and should be explored further.

ISSN:0736-0266    

DOI:10.1002/jor.1100170606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe intervertebral disc is the largest asvacular structure in the body; consequently, there are steep gradients in O2concentration, with PO2falling to as low as 1% O2in the centre of the disc. We investigated the effect of O2concentration on the rates of O2consumption, lactate production, and sulphate and proline incorporation in bovine caudal discs. We also investigated the effects of metabolic inhibitors of energy production pathways on tracer incorporation. Samples from the outer annulus and nucleus pulposus were incubated for 24 hours in 1‐21% O2. Rates were measured during the last 4 hours of incubation. As O2concentration was reduced from 10 to 1% O2, O2consumption rates fell by around 75% and lactate production rates almost doubled; the bovine discs thus showed a positive progressive Pasteur effect. Incorporation rates of [3H]proline and [35S]sulphate were lowest at 1% O2. In the nucleus, but not in the outer annulus, the rate of [35S]incorporation peaked at 5% O2, where it was 30% greater than at 21% O2and 150% greater than at 1% O2. The competitive glycolysis inhibitor 2‐deoxyglucose, the oxidative phosphorylation uncoupler 2,4‐dinitrophenol, and the oxidative phosphorylation inhibitor sodium azide all markedly reduced sulphate incorporation. These results, together with previous measurements of CO2production rates, suggest that a functionally significant fraction of the disc 's energy is supplied by oxidative phosphorylation. However, low levels of PO2, 2,4‐dinitrophenol, and sodium azide have been reported to reduce sulphate incorporation in articular cartilage, a tissue that derives its energy almost entirely from gly

ISSN:0736-0266    

DOI:10.1002/jor.1100170607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe goal of this study was to examine the simultaneous effects of mechanical compression of chondrocytes on mRNA expression and macromolecular synthesis of aggrrecan and type‐II collagen. Bovine cartilage explants were exposed to different magnitudes and durations of applied mechanical compression, and levels of aggrecan and type‐IIa collagen mRNA normalized to glyceraldehyde‐3‐phosphate dehydrogenase were measured and quantified by Northern blot analysis. Synthesis of aggrecan and type‐II collagen protein was measured by radiolabel incorporation of [35S]sulfate and [3H]proline into macromolecules. The results showed a dose‐dependent decrease in mRNA levels for aggrecan and type‐II collagen, with increasing compression relative to physiological cut thickness applied for 24 hours. Radiolabel incorporation into glycosaminoglycans and collagen also decreased with increasing compression in a dose‐related manner similar to the changes seen in mRNA expression. The modulation of aggrecan and type‐II collagen mRNA and protein synthesis were dependent on the duration of the compression. Aggrecan and type‐II collagen mRNA expression increased during the initial 0.5 hours of static compression; however, 4‐24 hours after compression was applied total mRNA levels had significantly decreased. The synthesis of aggrecan and collagen protein decreased more rapidly than did mRNA levels after the application of a step compression. Together, these results suggest that mechanical compression rapidly alters chondrocyte aggrecan and type‐II collagen gene expression on application of load. However, our results indicate that the observed decreases in biosynthesis may not be related solely to changes in mRNA expression. The mechanisms by which mechanical forces affect different segments of the biosynthetic pathways

ISSN:0736-0266    

DOI:10.1002/jor.1100170608

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractFrom 1986 to 1992, 88 patients with articular defects in the knee were treated with a perichondrial arthroplasty. In this study, we report on the results for 22 biopsies of grafted tissue with a mean follow‐up of 21 months. Biopsies were obtained at routine arthroscopy after approximately 1 year or at arthroscopy or arthrotomy at a later stage when patients were operated on again because of recurrent complaints. Biopsies were taken only when a partial failure was present or when there was a clear failure resulting in fibrocartilage, a loose flap, or a loose body. The biopsies were analyzed histologically, biochemically for the amount of type‐II collagen, and immunohistochemically with antibodies for types I, II, and X collagen. The well‐being of the patients was investigated with use of the Hospital for Special Surgery knee score. The biopsies from 6 patients contained more than 50% hyaline cartilage. At arthroscopy, the mean relative amount of type‐II collagen was 56% in the biopsies classified as good. The cartilage of the grafted area was macroscopically normal for eight of the 22 biopsies. Histological and biochemical analysis of biopsies from failed transplants showed fibrocartilage with mainly type‐I collagen. These tissues were retrieved primarily from patients with additional abnormalities in the knee joint. It was concluded that adult human perichondrium is able to form hyaline‐like cartilage in an isolated cartilage defect in an otherwise h

ISSN:0736-0266    

DOI:10.1002/jor.1100170609

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe effects of β‐aminopropionitrile, a known inhibitor of lysyl oxidase, on the extractability of newly synthesized collagen and integrative cartilage repair were determined in explant cultures of adult bovine articular cartilage. Dose‐escalation studies indicated that treatment of cartilage explants for 6 days with β‐aminopropionitrile caused a dose‐dependent inhibition of proteoglycan synthesis ([35S]sulfate incorporation) with a 50% inhibition at 2.2 mM. However, 0.25 mMβ‐aminopropionitrile had no detectable effect on proteoglycan synthesis and was thus used for subsequent experiments. Treatment of cartilage with β‐aminopropionitrile for 14 days increased the extractability of newly synthesized collagen with 4Mguanidine‐HCI while having little effect on proteoglycan synthesis, proteoglycan deposition, or cartilage cellularity (DNA content). In untreated cultures, the percentage of radiolabeled collagen ([3H]hydroxyproline) that was extractable after 1 day of radiolabeling, 6 days of radiolabeling, or 6 days of label and 6 days of chase decreased from 81 to 25 and 9%, respectively. In β‐aminopropionitrile‐treated cultures, the extractability was relatively higher (96, 62, and 47%, respectively). Treatment with β‐aminopropionitrile after radiolabeling with [14C]lysine also significantly inhibited the formation of the reducible crosslink [14C]dihydroxylysinonorleucine without affecting the overall deposition in cartilage of [14C]lysine and [14C]hydroxylysine. In functional repair studies, treatment with β‐aminopropionitrile caused an almost complete inhibition of integration between pairs of cartilage explants maintained in apposition for 2 weeks. These results indicate that β‐aminopropionitrile blocks the formation of collagen crosslinks in cartilage explants and suggest that such crosslinks are critical

ISSN:0736-0266    

DOI:10.1002/jor.1100170610

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractHyaluronic acid, recently renamed hyaluronan, has been used as a therapeutic intervention in the treatment of osteoarthritis. We have reported that high‐molecular‐weight (800 kDa) hyaluronan is effective in blocking the catabolic action of fibronectin fragments in explant cultures of bovine cartilage and in an experimentalin vivomodel of damage to the rabbit knee joint. The fibronectin fragments induce catabolic cytokines in human cartilage, which, in turn, suppress proteoglycan synthesis and induce matrix metalloproteinases to decrease the proteoglycan content. Since the clinical target of high‐molecular‐weight hyaluronan is human cartilage, which may differ in certain ways from bovine cartilage, we tested the effect on human knee cartilage. We found that 1 mg/ml hyaluronan completely blocked fibronectin fragment‐mediated decreases in proteoglycan content in five of five specimens of cartilage from the human knee. This was associated with binding of exogenous hyaluronan to the superficial surface, suppressed penetration of the fibronectin fragment into the cartilage, decreased expression for the first week in culture of one of the matrix metalloproteinases involved in cartilage degradation, matrix metalloproteinase‐3, and proteoglycan synthesis rates that increased to supernormal levels. However, the appearance of the NITEGE and VDIPEN neoepitopes, indices of cartilage degradation, was not blocked but was delayed by 1 week. The addition of hyaluronan to cartilage previously damaged by the fibronectin fragments or to osteoarthritic cartilage fully restored the proteoglycan content to control levels. We conclude that hyaluronan blocked damage at least partly by blocking penetration of the fibronectin fragments and slowing matrix metalloproteinase expression. However, the major effect on blocking damage and promoting repair may be through enhanced proteoglycan synthesis, a mechanism that requires further study. Nonetheless, these data clearly demonstrate that hyaluronan completely protected human cartilage in explant culture and facilitated a full restoration of proteoglycan in damage

ISSN:0736-0266    

DOI:10.1002/jor.1100170611

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY