Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prerequisite in defining the role of a growth factor in a disease is knowledge of its expression kinetics during the natural course of the disease. We, therefore, used immunohistochemical and immunoblot analyses to examine tissue distribution of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF-A) during the development of destructive arthropathy in the rat adjuvant arthritis model. In normal joints, bFGF was primarily localized in endothelial cells. In inflamed joints, increased staining for bFGF was found in the invading panni, hyperplastic synovium, and thickened periosteum where bFGF was also co-localized with two cell proliferation markers. Staining for bFGF began to increase at the onset of arthritis (days 11 to 13), reached peak level on days 17 to 24, and gradually declined afterward. In contrast, PDGF-A staining did not change until day 17 and the increased staining was restricted to areas of newly formed bone. The district temporal and spatial distribution pattern of these two growth factors during the destructive arthropathy strongly suggests that they play different roles during arthritis. Although PDGF-A seems to be exclusively related to osteogenesis, bFGF may have a more extensive impact on synovial proliferation and bone destruction as well as bone formation.
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PMID:Immunolocalization of basic fibroblast growth factor and platelet-derived growth factor-A during adjuvant arthritis in the Lewis rat. 797 44

Intraperitoneal injection of cell wall fragments from L. casei (ATCC 11578) induces an acute and a chronic inflammatory arthritis of the distal joints of LEW/N female rats. Histopathological changes in four distal joints and hematologic changes were analyzed on days 3, 10, 20, 30, 40, 50 and 59. All joints were scored for changes in inflammation, pannus, cartilage and bone. The acute inflammatory response consisted of fluid exudate, fibrin, neutrophils and some macrophages concentrated along the periosteum of the longer bones. The disease progressed with synovial fibroblast proliferation and infiltration of lymphocytes and macrophages. On day 10, cartilage changes were associated with pannus formation and subchondral fibrosis. Both localized bone resorption and periosteal new bone formation were features of the chronic phase. Lymphocytes were elevated above normal (p < 0.05) on day 3, 10, 20, 30 and 40; returning to the normal range on day 50 and 59. Neutrophils were elevated on days 10, 20, 30, 40 and 59. L. casei-induced polyarthritis in Lewis rats appears to be a fibroblast-, macrophage-mediated disease with a prominent lymphoid component.
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PMID:Pathogenesis of Lactobacillus casei-induced polyarthritis in Lewis rats: 1. Time related changes in histopathological scores and hematology. 827 62

Articular cartilage is both morphologically and biochemically heterogeneous. Its susceptibility to degenerative diseases such as arthritis and its limited repair capacity have made cartilage the focus of intense study; surprisingly, little is known of its development. Using a panel of specific antibodies, we have documented the temporal and spatial patterns of collagen types I, II, III, VI and X in the developing knee cartilage of the marsupial Monodelphis domestica from parturition to adulthood. Type I collagen was initially detected in the presumptive articular cartilage of the epiphyses in addition to the perichondrium. By 14 d postparturition, type I collagen was not detectable in the epiphyseal cartilage apart from insertion sites of ligaments and tendons of the joint. Similarly, type III collagen was detected at insertion sites of the major ligaments and tendons and within the perichondrium/periosteum but was never detected in the cartilage per se. Type II collagen was predictably distributed throughout the cartilage matrix and was also detected in the perichondrium. Type VI collagen was widely distributed throughout the cartilage matrix at parturition, but during development became restricted to a pericellular location particularly towards the presumptive articular cartilage, i.e. the epiphysis. Interestingly, generalised matrix immunopositivity was only retained in the hypertrophic cartilage of the secondary centre of ossification. After the formation of the secondary centre, type VI collagen became localised pericellularly in the deeper regions of the articular cartilage but was absent in the cartilage of the growth plate. Type X collagen showed a novel distribution pattern. In addition to being synthesised by hypertrophic chondrocytes, this collagen type was also expressed transiently by some cells at the presumptive articular surface. Furthermore, these surface chondrocytes also stained histochemically for alkaline phosphatase, suggesting that they were terminally differentiated. The fate of these terminally differentiated cells is unknown.
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PMID:The development of articular cartilage: I. The spatial and temporal patterns of collagen types. 918 84

Members of the TGF-beta superfamily are important regulators of skeletal development. TGF-betas signal through heteromeric type I and type II receptor serine/threonine kinases. When over-expressed, a cytoplasmically truncated type II receptor can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR). To determine the role of TGF-betas in the development and maintenance of the skeleton, we have generated transgenic mice (MT-DNIIR-4 and -27) that express the DNIIR in skeletal tissue. DNIIR mRNA expression was localized to the periosteum/perichondrium, syno-vium, and articular cartilage. Lower levels of DNIIR mRNA were detected in growth plate cartilage. Transgenic mice frequently showed bifurcation of the xiphoid process and sternum. They also developed progressive skeletal degeneration, resulting by 4 to 8 mo of age in kyphoscoliosis and stiff and torqued joints. The histology of affected joints strongly resembled human osteo-arthritis. The articular surface was replaced by bone or hypertrophic cartilage as judged by the expression of type X collagen, a marker of hypertrophic cartilage normally absent from articular cartilage. The synovium was hyperplastic, and cartilaginous metaplasia was observed in the joint space. We then tested the hypothesis that TGF-beta is required for normal differentiation of cartilage in vivo. By 4 and 8 wk of age, the level of type X collagen was increased in growth plate cartilage of transgenic mice relative to wild-type controls. Less proteoglycan staining was detected in the growth plate and articular cartilage matrix of transgenic mice. Mice that express DNIIR in skeletal tissue also demonstrated increased Indian hedgehog (IHH) expression. IHH is a secreted protein that is expressed in chondrocytes that are committed to becoming hypertrophic. It is thought to be involved in a feedback loop that signals through the periosteum/ perichondrium to inhibit cartilage differentiation. The data suggest that TGF-beta may be critical for multifaceted maintenance of synovial joints. Loss of responsiveness to TGF-beta promotes chondrocyte terminal differentiation and results in development of degenerative joint disease resembling osteoarthritis in humans.
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PMID:Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. 933 55

Methionine-enkephalin (met-enk), an endogenous opiate, mimics many of the effects of morphine by binding to opiate receptors, thereby eliciting similar cellular and behavioral effects. Using biochemical and immunohistochemical techniques, several peptides have been identified in bone and joint tissues. Here we report, for the first time, the presence as well as concentration of met-enk in bone and joint tissues. Immunohistochemistry using electron and immunofluorescence microscopy showed cellular and neuronal distribution of met-enk in bone and joint tissues. The concentration of met-enk analyzed by high performance liquid chromatography electrochemical detection or radioimmunoassay was high in bone marrow, periosteum, ankle joint tissue, and cortical bone. Analysis by fast atom bombardment mass spectrometry suggested that the recovered fragment was met-enk Administration of met-enk inhibits osteoblast cell growth in culture, which is reversible by naltrexone. In arthritic rats, the concentration of met-enk was significantly decreased in ankle joints compared with controls, suggesting a role for met-enk in the pathophysiology of adjuvant arthritis.
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PMID:Methionine-enkephalin in bone and joint tissues. 944 94

The localization of neurokinin A (NK-A) in the normal ankle joint of rats was investigated by an immunoelectron microscopic technique with specific antisera to NK-A. Immunoreactivity was detected in bone matrix, myelinated nerve fiber in the periosteum, and bone marrow and synovial cells. No immunoreactivity was observed in osteoblasts, osteocytes, and osteoclasts. Using radioimmunoassay (RIA), a detectable concentration of NK-A was observed in the bone marrow, periosteum, cortical bone, and ankle of normal rats. In rats with chronic adjuvant arthritis, induced by intradermal injection of mycobacterium butyricum in paraffin oil into the base of the tail, the concentrations of NK-A using RIA in ankles and spinal cords were found to be significantly increased compared with acute or control rats. There were no significant differences between the latter two. Similarly, increased NK-A labeling was observed using immunoelectron microscopy in bone matrix and bone marrow monocyte cells of the chronic arthritic rats. These findings indicate the existence of as well as a biological role of NK-A in bone and joint tissues.
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PMID:Neurokinin-A in bone and joint tissues: changes in adjuvant arthritis. 989 68

Lower numbers of neuropeptide-containing fibers in arthritic joints have been found as compared to control joints. This may be the result of fiber depletion, necrosis of fibers, or proliferation of soft tissues without neural sprouting. To discriminate between these possibilities, we studied the relationships between soft tissue proliferation, changes in vascularity of synovial tissues, and changes in joint innervation during arthritis. Arthritis was induced in the knee joint of mice by a single subpatellar injection of methylated bovine serum albumin after previous immunization. Antibodies to protein gene product 9.5, S-100, and growth-associated protein-43 (GAP-43) were used to study the general innervation pattern. Antibodies to calcitonin gene-related peptide (CGRP), vasointestinal polypeptide (VIP), substance P (SP), and tyrosine hydroxylase (TH) were used to localize sensory (SP, CGRP, VIP) and sympathetic (TH) fibers. Blood vessels of the joint were studied with ink perfusion, GAP-43, and a vascular marker (LF1). Directly after the induction of arthritis, the synovial cavity was enlarged and filled with leukocytes. From day 4 onward, small sprouting blood vessels penetrated the avascular mass of cells in the joint cavity. After 1 week, the vascular sprouting activity and GAP-43 immunoreactivity were maximal, and after 2 weeks, vascular sprouting activity diminished. In the subsequent period, the synovia slowly regained their prearthritic appearance and thickness. The most pronounced changes in the general staining pattern of CGRP, SP, VIP, and TH were found in the periosteum. From 2 days to 4 weeks after the induction of arthritis, the layer of SP, CGRP, and VIP fibers in the femoral periosteum was thicker and more irregular. GAP-43 staining showed many terminal varicosities, which suggested sprouting of nerve fibers. From 2 days to 2 weeks after the induction of arthritis, the SP and CGRP fibers in the periosteum showed gradual depletion. In the thickened subsynovial tissues that were revascularized, no ingrowth of neural elements was found. As the total number of nerve fibers in the synovial tissue did not change, large parts of the synovia directly facing the joint cavity were not innervated at 1 week after the induction of arthritis. These results strongly suggest that periosteal SP and CGRP fibers were depleted during arthritis. Synovial proliferation without concomitant fiber growth is the main cause of the reduced number of immunocytochemically detectable fibers in the mouse arthritic knee joint.
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PMID:Neurovascular plasticity in the knee joint of an arthritic mouse model. 1096 36

Several alphaviruses, including the Sindbis-group viruses, Ross River virus, O'nyong-nyong virus, and Chikungunya virus, are associated with outbreaks of acute and persistent arthralgia and arthritis in humans. Mechanisms underlying alphavirus-induced arthralgia and arthritis are not clearly understood, though direct viral replication within or around the affected joints is thought to contribute to disease. S.A.AR86 is a Sindbis-group alphavirus closely related to the arthralgia-associated Ockelbo and Girdwood S.A viruses. Following inoculation with S.A.AR86 derived from a molecular clone, infectious virus was isolated from bone and joint tissue 1 to 6 days postinfection. Studies using either in situ hybridization or S.A.AR86-derived double promoter viruses and replicons expressing green fluorescent protein localized sites of viral replication to the periosteum, tendons, and endosteum within the epiphyses of the long bones adjacent to articular joints. These results demonstrate that alphaviruses associated with arthralgia in humans replicate within bone-associated connective tissue adjacent to articular joints in an adult mouse model.
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PMID:Sindbis-group alphavirus replication in periosteum and endosteum of long bones in adult mice. 1098 76

Periosteal hyperostosis (exostosis) was identified in 5.9% (11/188) of DBA/1 male mice 10-14 weeks old used for collagen-induced arthritis (CIA) efficacy testing of immunomodulatory biologics. Mice with and without CIA in the affected limb, and also control and treated groups, were involved, with bilateral lesions in one mouse. Hyperostosis was characterized by circumferential and raised masses of variable location, length, and laterality, generally external to but occasionally breaching the periosteum of the metatarsals, metacarpals, tibia, femur, and humerus. Proportionally, the hyperostotic foci consisted of cancellous and woven bone, followed by osteoid, cartilage, and fibrous connective tissue and rarely inflammatory cells. A displaced, presumably pathological fracture with callus formation was a concurrent lesion in only one case. Tartrate-resistant acid phosphatase-positive cells were frequent at bony interfaces, indicating an active resorptive process. Periosteal hyperostosis is an incidental and potentially common finding in DBA/1 mice. Underreporting may occur due to the male bias in disease expression of this CIA model, sampling bias (generally paws only), tissue obliteration in the presence of CIA, and lack of comprehensive historical data on the background and aging lesions in this strain of mouse. Identification of such confounding bony lesions is important to the interpretation of efficacy studies, and suggests the need to further examine the biology of bone development in this strain of mouse.
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PMID:Periosteal hyperostosis (exostosis) in DBA/1 male mice. 1205 56

To study the level of leu-enkephalin in bone and joint tissues and in the spinal cord of rats with adjuvant arthritis, arthritis was induced in Lewis rats by the injection of Mycobacterium butyricum in Freund's incomplete adjuvant (FIA). Immunoelectron microscopy (IEM) was used to monitor the cellular distribution of leu-enkephalin in control and arthritis groups, and radioimmunoassay (RIA) was used to measure the concentration in the tissues. The results of IEM showed increased levels of leu-enkephalin in the matrix of the sciatic nerve, in nerve fibres in the synovial membrane and periosteum, as well as in fibroblasts and endothelial cells of the periosteum in arthritic groups. In macrophage-like cells of the synovial membrane as well as monocyte and polymorphonuclear lineage cells in the bone marrow, the level of leu-enkephalin was decreased in the arthritic group. The results of RIA showed that the concentration of leu-enkephalin was lower in the ankle and increased in the spinal cord of arthritic animals compared with controls. In conclusion, leu-enkephalin levels were decreased in joints and in bone marrow, but increased in nerve tissues in the group with arthritis. Further studies are needed to show whether leu-enkephalin is involved in a process that serves to limit the effect of immunisation.
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PMID:Tissue levels of leu-enkephalin in rats with adjuvant arthritis. 1558 35


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