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Joint Tissue (joint + tissue)
Selected AbstractsFunctional adaptation of the femoral head to voluntary exerciseTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2006Jeffrey H. Plochocki Abstract The functional adaptation of limb joints during postnatal ontogeny is necessary to maintain proper joint function. Joint form is modified primarily through differential rates of articular cartilage proliferation across articular surfaces during endochondral growth. This process is hypothesized to be mechanically regulated by the magnitude and orientation of stresses in the articular cartilage. However, the adaptation of limb joint morphology to the mechanical environment is poorly understood. We investigate the effects of voluntary exercise on femoral head morphology in 7-week-old female mice of the inbred strain C57BL/6J. The mice were divided into a control group and a group treated with voluntary access to an activity wheel for the duration of the 4-week study. Histomorphometric comparisons of chondral and osseous joint tissue of the proximal femur were made between control and exercise treatment groups. We find that exercised mice have significantly thicker articular cartilage with greater chondral tissue area and cellularity. Exercised mice also exhibit significantly greater bone tissue area and longer and flatter subchondral surfaces. No significant difference is found in the curvature of the articular cartilage or the length of the chondral articular surface between groups. These data suggest that a complex mechanistic relationship exists between joint stress and joint form. Joint tissue response to loading is multifaceted, involving both size and shape changes. Our data support the hypothesis that joint growth is ontogenetically plastic. Mechanical loading significantly influences chondral and subchondral tissue proliferation to provide greater support against increased mechanical loading. Anat Rec Part A, 288A:776,781, 2006 © 2006 Wiley-Liss, Inc. [source] Age-Related Mitochondrial DNA Mutations in the Human LarynxTHE LARYNGOSCOPE, Issue 12 2000Jose M. Manaligod MD Abstract Objective To determine whether age-related mitochondrial DNA mutations occur in the human larynx. Study Design Genetic study of cadaveric larynx specimens. Methods Vocal fold mucosa, thyroarytenoid muscle, and cricoarytenoid joint tissue were harvested from 13 fresh postmortem larynges (age range, 2 d,82 y). DNA was extracted from each sample, and the polymerase chain reaction (PCR) was used to amplify a target DNA sequence resulting from the common age-associated, 4977,base-pair (bp) mitochondrial DNA deletion. PCR products were visualized by agarose gel electrophoresis. Automated sequencing determined the sequence of identified PCR products. Subjects Thirteen cadaveric larynges were obtained through the University of Kentucky Medical Center (Lexington, KY). Specimens from patients with a history of head and neck cancer, previous laryngeal trauma, or surgery were excluded. Results Strongly positive bands were identified in samples from three individuals. Weaker bands were seen in samples from four other samples. No band was noted from the two pediatric larynges. Different band patterns were seen among the three different tissue sites in the larynges with positive PCR products, but no consistent pattern was seen. Sequencing of the identified PCR products from selected samples confirmed that they were products of the age-associated, 4977-bp mitochondrial DNA deletion. Conclusions An age-associated mitochondrial DNA deletion was detected in several postmortem human larynges. Its presence seemed to increase in appearance with age. In the larynges in which the deletion occurred, there were individual regional differences in the occurrence of the deletion, but no consistent pattern was noted across all individuals who carried the deletion. [source] Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain modelARTHRITIS & RHEUMATISM, Issue 10 2010Hee-Jeong Im Objective To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain. Methods An animal model of knee joint OA pain was generated by intraarticular injection of mono-iodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord. Results We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA. Conclusion Our results indicate that MIA-induced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain. [source] Follistatin-like protein 1 is a mesenchyme-derived inflammatory protein and may represent a biomarker for systemic-onset juvenile rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 8 2010David C. Wilson Objective To examine both the source of follistatin-like protein 1 (FSTL-1) and the factors that induce its expression in arthritis, and to determine whether juvenile rheumatoid arthritis (JRA) is characterized by overexpression of FSTL-1. Methods FSTL-1 expression patterns were analyzed by immunohistochemical staining of joint tissue derived from mice with collagen-induced arthritis. Induction of FSTL-1 secretion was assessed in osteoblasts, adipocytes, and human fibroblast-like synoviocytes in response to transforming growth factor , (TGF,), interleukin-1, (IL-1,), tumor necrosis factor , (TNF,), and IL-6. In addition, sera and synovial fluid from children with oligoarticular, polyarticular, or systemic-onset JRA were assayed for FSTL-1 using a custom enzyme-linked immunosorbent assay. FSTL-1 concentrations in these patients were assessed for correlations with the erythrocyte sedimentation rate (ESR) and platelet count. Results Immunohistochemical staining of murine joint sections demonstrated expression of FSTL-1 in all cell types of the mesenchymal lineage, including osteocytes, chondrocytes, adipocytes, and fibroblasts. FSTL-1 could be induced in osteoblasts, adipocytes, and human fibroblast-like synoviocytes by TGF,, IL-1,, TNF,, and IL-6. The IL-1, response was significantly greater than the TNF, response (P < 0.05). In human serum and synovial fluid, only those samples from children with the systemic-onset JRA subtype had elevated concentrations of FSTL-1. The synovial fluid concentrations of FSTL-1 were 2,3-fold higher than the serum concentrations. The elevation in serum FSTL-1 concentrations seen in children with systemic-onset JRA correlated closely with elevations in the ESR and platelet count. Conclusion These findings demonstrate that the arthritic joint matrix is a major source of FSTL-1 and that IL-1, is a central mediator of FSTL-1 secretion. Furthermore, FSTL-1 may represent a useful biomarker of disease activity in systemic-onset JRA. [source] Mechanical injury potentiates proteoglycan catabolism induced by interleukin-6 with soluble interleukin-6 receptor and tumor necrosis factor , in immature bovine and adult human articular cartilageARTHRITIS & RHEUMATISM, Issue 10 2009Yihong Sui Objective Traumatic joint injury can damage cartilage and release inflammatory cytokines from adjacent joint tissue. The present study was undertaken to study the combined effects of compression injury, tumor necrosis factor , (TNF,), and interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on immature bovine and adult human knee and ankle cartilage, using an in vitro model, and to test the hypothesis that endogenous IL-6 plays a role in proteoglycan loss caused by a combination of injury and TNF,. Methods Injured or uninjured cartilage disks were incubated with or without TNF, and/or IL-6/sIL-6R. Additional samples were preincubated with an IL-6,blocking antibody Fab fragment and subjected to injury and TNF, treatment. Treatment effects were assessed by histologic analysis, measurement of glycosaminoglycan (GAG) loss, Western blot to determine proteoglycan degradation, zymography, radiolabeling to determine chondrocyte biosynthesis, and Western blot and enzyme-linked immunosorbent assay to determine chondrocyte production of IL-6. Results In bovine cartilage samples, injury combined with TNF, and IL-6/sIL-6R exposure caused the most severe GAG loss. Findings in human knee and ankle cartilage were strikingly similar to those in bovine samples, although in human ankle tissue, the GAG loss was less severe than that observed in human knee tissue. Without exogenous IL-6/sIL-6R, injury plus TNF, exposure up-regulated chondrocyte production of IL-6, but incubation with the IL-6,blocking Fab significantly reduced proteoglycan degradation. Conclusion Our findings indicate that mechanical injury potentiates the catabolic effects of TNF, and IL-6/sIL-6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNF, appeared partly due to endogenous IL-6, since GAG loss was partially abrogated by an IL-6,blocking Fab. [source] Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: Prominent role of Wnt-induced signaling protein 1ARTHRITIS & RHEUMATISM, Issue 2 2009Arjen B. Blom Objective Wnt signaling pathway proteins are involved in embryonic development of cartilage and bone, and, interestingly, developmental processes appear to be recapitulated in osteoarthritic (OA) cartilage. The present study was undertaken to characterize the expression pattern of Wnt and Fz genes during experimental OA and to determine the function of selected genes in experimental and human OA. Methods Longitudinal expression analysis was performed in 2 models of OA. Levels of messenger RNA for genes from the Wnt/,-catenin pathway were determined in synovium and cartilage, and the results were validated using immunohistochemistry. Effects of selected genes were assessed in vitro using recombinant protein, and in vivo by adenoviral overexpression. Results Wnt-induced signaling protein 1 (WISP-1) expression was strongly increased in the synovium and cartilage of mice with experimental OA. Wnt-16 and Wnt-2B were also markedly up-regulated during the course of disease. Interestingly, increased WISP-1 expression was also found in human OA cartilage and synovium. Stimulation of macrophages and chondrocytes with recombinant WISP-1 resulted in interleukin-1,independent induction of several matrix metalloproteinases (MMPs) and aggrecanase. Adenoviral overexpression of WISP-1 in murine knee joints induced MMP and aggrecanase expression and resulted in cartilage damage. Conclusion This study included a comprehensive characterization of Wnt and Frizzled gene expression in experimental and human OA articular joint tissue. The data demonstrate, for the first time, that WISP-1 expression is a feature of experimental and human OA and that WISP-1 regulates chondrocyte and macrophage MMP and aggrecanase expression and is capable of inducing articular cartilage damage in models of OA. [source] Targeted mast cell silencing protects against joint destruction and angiogenesis in experimental arthritis in miceARTHRITIS & RHEUMATISM, Issue 6 2007Manfred Kneilling Objective Induction of arthritis with autoantibodies against glucose-6-phosphate isomerase (GPI) is entirely independent of T cells and B cells but is strictly dependent on the presence of mast cells. Here, we used this disease model to analyze whether exclusive intraarticular mast cell reconstitution is sufficient for disease induction and whether targeted mast cell silencing can prevent neoangiogenesis and joint destruction, 2 hallmarks of rheumatoid arthritis. Methods Ankle swelling and clinical index scores were determined after injection of either K/BxN mouse,derived serum or control serum in wild-type Kit+/Kit+ mice, congenic mast cell,deficient KitW/KitW - v mice, or mast cell,deficient KitW/KitW - v mice reconstituted with mast cells, either by intraperitoneal or selective intraarticular injection. Angiogenesis was quantified in vivo by measuring activated ,v,3 integrin using 18F,galacto-RGD and positron emission tomography. In addition, staining of joint tissue with hematoxylin and eosin, Giemsa, ,3, and ,-actin was performed. The effect of mast cell stabilization by treatment with cromolyn or salbutamol was investigated in C57BL/6 or BALB/c mice. Results Comparing wild-type mice, mast cell,deficient KitW/KitW - v mice, and mast cell,reconstituted KitW/KitW - v mice, we first showed that intraarticular and intraperitoneal mast cell engraftment fully restores susceptibility to antibody-induced arthritis, angiogenesis, and ,v,3 integrin activation. Importantly, selective mast cell silencing with either salbutamol or cromolyn prevented ,v,3 integrin activation, angiogenesis, and joint destruction. Conclusion Mast cell engraftment fully restores susceptibility to ,v,3 integrin activation, angiogenesis, and joint destruction in GPI antibody,induced arthritis. Importantly, selective mast cell stabilization prevents ,v,3 integrin activation, angiogenesis, and joint destruction. [source] Inhibition of adjuvant-induced arthritis by systemic tissue inhibitor of metalloproteinases 4 gene deliveryARTHRITIS & RHEUMATISM, Issue 12 2002Mahmut Y. Çeliker Objective An imbalance in the matrix metalloproteinase:tissue inhibitor of metalloproteinases (MMP:TIMP) ratio in favor of MMP appears to be an important determinant of tissue damage in arthritis. We undertook this study to explore whether reversal of this imbalance in favor of TIMP would alter this process and to examine the mechanism of this alteration. Methods We administered human TIMP-4 by electroporation-mediated intramuscular injection of naked DNA using the rat adjuvant-induced arthritis (AIA) model. Results Intramuscular naked TIMP-4 gene administration resulted in high circulating TIMP-4 levels and completely abolished arthritis development in the rat AIA model. This inhibition was associated with significantly decreased MMP activity in the joint tissue as well as with significantly decreased serum and tissue tumor necrosis factor , levels and serum interleukin-1, levels compared with animals with arthritis. The mutation of cysteine at position 1 of TIMP-4 failed to block the development of AIA. Conclusion Our data indicate that TIMP-4 is a potent antiinflammatory agent, and that its antiarthritis function may be mediated by MMPs. Arthritis-inhibiting effects of TIMP-4 may suggest a unique application of this gene therapy method for arthritis. [source] Effect of heparinoid on the production of tissue inhibitor of metalloproteinases (TIMP)-3 in rheumatoid synovial fibroblastsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2002Hideki Watanabe Heparinoid is one of the major contents of Mobilat widely used as an antirheumatic drug. To clarify the precise mechanisms of the antirheumatic effect of heparinoid, we investigated its effects on the production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) from rheumatoid synovial fibroblasts stimulated (or not) with interleukin-1 alpha (IL-1,) at 100 units mL,1. The expression of TIMP-3 mRNA was also investigated in a similar manner. The production of both MMPs and TIMPs and the expression of TIMP-3 mRNA were investigated by western-blot analysis and northern-blot hybridization, respectively. Under the stimulation of IL-1,, heparinoid increased the production of TIMP-3 in a concentration-dependent manner, but not TIMP-1, TIMP-2, MMP-1 or MMP-3. Heparinoid did not affect the expression of TIMP-3 mRNA that was increased by the stimulation of IL-1,. These findings suggest that the anti-rheumatoid effect of heparinoid may be due to increased production of TIMP-3. This increase in TIMP-3 may help redress the imbalance between the amounts of MMPs and TIMPs as observed in the joint tissues of rheumatoid arthritis and osteoarthritis patients. [source] Virtual biopsy of the joint tissues using near-infrared, reflectance confocal microscopy.MICROSCOPY RESEARCH AND TECHNIQUE, Issue 10 2006A pilot study Abstract Standard noninvasive imaging techniques applied to joints provide gross morphological features, insufficient for assessing histological detail. On the other hand, biopsying is invasive, time consuming, and may involve unwanted processing artifacts. Near-infrared reflectance confocal microscopy is a technique that allows serial, high-resolution optical sectioning through intact tissues without employing exogenous fluorescent stains. The aim of this work was to evaluate the potential utility of near-infrared reflectance confocal microscopy for providing immediate histological information on meniscus, articular cartilage, epiphyseal plate, bone, muscle, and tendon. Images from near-infrared reflectance confocal microscopy were compared with mirror routine histology sections. Characteristic architectural features were readily visualized in the three dimensions of space. Additionally, the use of experimental contrast agents highlighted the localization of nuclei. Limitations include penetration depth and minor optical artifacts. In conclusion, near-infrared reflectance confocal microscopy is a useful technique for immediate, nondestructive, serial "virtual" sectioning through intact tissues, being thus a potential adjunct to current imaging techniques in orthopedics. Microsc. Res. Tech., 2006. © 2006 Wiley-Liss, Inc. [source] Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytesARTHRITIS & RHEUMATISM, Issue 5 2007Chinh N. Tran Objective To assess the ability of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to function as antigen-presenting cells (APCs) for arthritogenic autoantigens found within inflamed joint tissues. Methods Human class II major histocompatibility complex (MHC),typed FLS were used as APCs for murine class II MHC,restricted CD4 T cell hybridomas. Interferon-, (IFN,),treated, antigen-loaded FLS were cocultured with T cell hybridomas specific for immunodominant portions of human cartilage gp-39 (HC gp-39) or human type II collagen (CII). T cell hybridoma activation was measured by enzyme-linked immunosorbent assay of culture supernatants for interleukin-2. Both synthetic peptide and synovial fluid (SF) were used as sources of antigen. APC function in cocultures was inhibited by using blocking antibodies to human class II MHC, CD54, or CD58, or to murine CD4, CD11a, or CD2. Results Human FLS could present peptides from the autoantigens HC gp-39 and human CII to antigen-specific MHC-restricted T cell hybridomas. This response required pretreatment of FLS with IFN,, showed MHC restriction, and was dependent on human class II MHC and murine CD4 for effective antigen presentation. Furthermore, FLS were able to extract and present antigens found within human SF to both the HC gp-39 and human CII T cell hybridomas in an IFN,-dependent and MHC-restricted manner. Conclusion RA FLS can function as APCs and are able to present peptides derived from autoantigens found within joint tissues to activated T cells in vitro. In the context of inflamed synovial tissues, FLS may be an important and hitherto overlooked subset of APCs that could contribute to autoreactive immune responses. [source] | ||||||||||