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

In this study we examined the effect of ribbon-type (circular-type) NF-kappaB decoy oligodeoxynucleotides (RNODN) on osteoclast induction and activity. We extracted bone marrow cells from the femurs of rats and incubated non-adherent cells with receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). First, transfer efficiency into osteoclasts and their precursors, resistance to exonuclease, and binding activity of decoy to NF-kappaB were examined. Next, to examine the effect of RNODN on osteoclast induction and activity, osteoclast differentiation and pit formation assays were performed. RNODN were injected into the ankle joints of rats with collagen-induced arthritis. Joint destruction and osteoclast activity were examined by histological study. The resistance of RNODN to exonuclease and their binding activity on NF-kappaB were both greater than those of phosphorothionated NF-kappaB decoy oligodeoxynucleotides. The absolute number of multinucleate cells scoring positive for tartrate-resistant acid phosphatase was significantly decreased in the RNODN-treated group. The average calcified matrix resorbed area was significantly decreased in the RNODN-treated group. Histological study showed marked suppression of joint destruction and osteoclast activity by intra-articular injection of RNODN. These results suggest the inhibitory effect of RNODN on the induction and activity of osteoclasts. Direct intra-articular injection of RNODN into the joints may be an effective strategy for the treatment of arthritis.
Arthritis Res Ther 2006
PMID:Inhibitory effect of ribbon-type NF-kappaB decoy oligodeoxynucleotides on osteoclast induction and activity in vitro and in vivo. 1681 65

We investigated the time-course changes in bone destruction in rats with collagen-induced arthritis (CIA). The synovial-cartilage junction (SCJ) and epiphyseal bone marrow of the femoral posteromedial condyle in CIA rats were evaluated histologically and immunohistologically at 2, 3, 4, 6, and 8 weeks after sensitization. Two weeks after sensitization, tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells formed resorption lacunae on the lateral side of the cortical bone under the SCJ. No resorption lacunae were observed in bone marrow. Three weeks after sensitization, resorption lacunae on the lateral side of the cortical bone expanded, but no bone marrow invasion by pannus was observed. In bone marrow, many TRAP-positive multinuclear cells appeared and formed resorption lacunae in subchondral bone. Four weeks after sensitization, cortical bone was destroyed, and pannus had invaded the bone marrow. After six weeks, trabecular bone and subchondral bone plate were extensively resorbed by TRAP-positive cells. Bone destruction in CIA began with the appearance of TRAP-positive cells on the lateral side of the cortical bone under the SCJ, followed by the TRAP-positive multinuclear cells in bone marrow, which were morphologically unconnected to the SCJ lesions. These histological findings suggested that bone destruction in the early stage of arthritis occurred in two anatomically different regions.
 ...
PMID:Tartrate-resistant acid phosphatase-positive cells in the synovial-cartilage junction and bone marrow during the progression of collagen-induced arthritis in adult rats. 1714 61

Patients with rheumatoid arthritis commonly suffer both systemic and periarticular osteoporosis. Bisphosphonates (BPs) are inhibitors of bone resorption, and several derivatives have been developed for treatment of enhanced bone resorption. We aimed to characterize osteoclast formation in two different sites, the proximal tibial and distal tibial areas, in rats with adjuvant arthritis, and to investigate the impact of amino or non-amino types of bisphosphonate. Adjuvant arthritis was initiated in rats while administering daily injections of either etidronate, a non-amino BP, or alendronate, an amino BP, for 3 weeks. On the day following the last injection, bone mineral density (BMD) was measured in the proximal tibia to assess systemic osteoporosis and in the distal tibia for periarticular osteoporosis using dual-energy X-ray absorptiometry. Subsequently, bone marrow cells from either end of the tibia were collected and incubated for 7 days before staining and counting tartrate-resistant acid phosphatase positive cells. In the rats with adjuvant arthritis, BMD of either end of the tibia was lower than in normal rats. Although etidronate prevented bone mineral loss at both ends, distal loss was significantly less than proximal. In contrast, alendronate significantly inhibited mineral loss primarily in the proximal area. Large osteoclasts, defined as having five or more nuclei, formed preferentially in the proximal tibia, while small osteoclasts with fewer than four nuclei were found mainly distally. The suppressive effect of alendronate was greater on the large osteoclasts, while etidronate had a greater effect on the small osteoclasts. These results show that the size and multinuclearity of osteoclasts and the number of osteoclasts formed are different in the distal and proximal areas of the tibia, and that alendronate and etidronate may suppress different types of osteoclasts as discriminated by the number of nuclei.
 ...
PMID:Differences in osteoclast formation between proximal and distal tibial osteoporosis in rats with adjuvant arthritis: inhibitory effects of bisphosphonates on osteoclasts. 1716 94

Dendritic cells (DC) are the mononuclear cells that initiate adaptive immune responses. Osteoclasts (OC) are the multinucleated giant cells that resorb bone. As previously described for human conventional DC (cDC), we demonstrate that murine cDC, either in vitro generated from Fms-like tyrosine kinase 3 (Flt3)+ bone marrow progenitors or ex vivo purified from spleen, are able to develop into OC in response to M-CSF and receptor activator of NF-kappaB ligand (RANKL) in vitro. This transdifferentiation is driven by the immune environment that controls cDC maturation, cell fusion, tartrate-resistant acid phosphatase (TRAP) and bone resorption activities. Only immature cDC have the capacity to become OC since mature cDC or plasmacytoid DC do not. Additions of the pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, or human rheumatoid synovial fluid, increase murine cDC transdifferentiation into OC, whereas IFN-alpha inhibits it. The adaptive cytokine, IFN-gamma, inhibits cDC fusion while IL-4 increases it. IL-2, IFN-gamma and IL-4 inhibit TRAP and bone resorption activities contrary to IL-10, which enhances both activities. A putative new "immune multinucleated giant cell" unable to resorb bone, which is formed owing to IL-4, is underlined. The future analysis of cDC transdifferentiation into OC in murine models of inflammatory arthritis will give us the quantitative importance of this phenomenon in vivo.
 ...
PMID:Murine dendritic cell transdifferentiation into osteoclasts is differentially regulated by innate and adaptive cytokines. 1730 26

Aseptic loosening of a joint prosthesis is associated with remodelling of bone tissue in the vicinity of the prosthesis. In the present study, we investigated the effects of synovial fluid (SF) from patients with a loose prosthetic component and periprosthetic osteolysis on osteoclast and osteoblast activities in vitro and made comparisons with the effects of SF from patients with osteoarthritis (OA). Bone resorption was assessed by the release of calcium 45 (45Ca) from cultured calvariae. The mRNA expression in calvarial bones of molecules known to be involved in osteoclast and osteoblast differentiation was assessed using semi-quantitative reverse transcription-polymerase chain reaction (PCR) and real-time PCR. SFs from patients with a loose joint prosthesis and patients with OA, but not SFs from healthy subjects, significantly enhanced 45Ca release, effects associated with increased mRNA expression of calcitonin receptor and tartrate-resistant acid phosphatase. The mRNA expression of receptor activator of nuclear factor-kappa-B ligand (rankl) and osteoprotegerin (opg) was enhanced by SFs from both patient categories. The mRNA expressions of nfat2 (nuclear factor of activated T cells 2) and oscar (osteoclast-associated receptor) were enhanced only by SFs from patients with OA, whereas the mRNA expressions of dap12 (DNAX-activating protein 12) and fcrgamma (Fc receptor common gamma subunit) were not affected by either of the two SF types. Bone resorption induced by SFs was inhibited by addition of OPG. Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity. The mRNA expression of alkaline phosphatase and osteocalcin was increased by SFs from patients with OA, whereas only osteocalcin mRNA was increased by SFs from patients with a loose prosthesis. Our findings demonstrate the presence of a factor (or factors) stimulating both osteoclast and osteoblast activities in SFs from patients with a loose joint prosthesis and periprosthetic osteolysis as well as in SFs from patients with OA. SF-induced bone resorption was dependent on activation of the RANKL/RANK/OPG pathway. The bone-resorbing activity could not be attributed solely to any of the known pro-inflammatory cytokines, well known to stimulate bone resorption, or to RANKL or prostaglandin E2 in SFs. The data indicate that SFs from patients with a loose prosthesis or with OA stimulate bone resorption and that SFs from patients with OA are more prone to enhance bone formation.
Arthritis Res Ther 2007
PMID:Effects on osteoclast and osteoblast activities in cultured mouse calvarial bones by synovial fluids from patients with a loose joint prosthesis and from osteoarthritis patients. 1731 39

We investigated the inhibitory mechanism of bone resorption by minodronic acid in collagen-induced arthritis (CIA) in rats. Four groups of female Sprague-Dawley rats, aged 7 months, were studied: three groups of collagen-sensitized rats, including one placebo-administered group (CIA-P), and two minodronic acid-administered groups at 0.2 mg/kg/2 day (CIA-BIS) and 2.0 mg/kg/2 day (CIA-BIS10). These were studied with an additional untreated observation group (Cont group). Minodronic acid was administered orally a day after the initial sensitization. The femoral posteromedial condyle was analyzed histologically and immunohistologically 4 weeks after the initial sensitization. Western blotting was also performed to assess the receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression of the knee joints. In CIA-P rats, many tartrate-resistant acid phosphatase (TRAP)-positive cells were found at the pannus-lining layer and the epiphyseal medulla. The bone-lining cells in the epiphyseal medulla and the cells in the pannus strongly expressed RANK and RANKL. In the minodronic acid-administered group, the number of TRAP-positive cells and the severity of arthritis were reduced. The reduction in the CIA-BIS10 group was significant compared with the CIA-P group (P < 0.05). Dosage-dependent reduction of RANK and RANKL expression was confirmed by immunohistology and Western blotting. With or without minodronic acid administration, no apoptotic cells were found in any groups using the TdT-mediated dUTP-biotinnick end labeling (TUNEL) method. The expression of OPG was not clear in all groups. These results demonstrated that minodronic acid inhibited the differentiation and the activation of osteoclasts not by inducing apoptosis but by inhibiting the RANKL-RANK system, and thereby suppressing bone resorption.
 ...
PMID:Minodronic acid influences receptor activator of nuclear factor kappaB ligand expression and suppresses bone resorption by osteoclasts in rats with collagen-induced arthritis. 1756 74

Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.
 ...
PMID:Expression of immune response genes in the stifle joint of dogs with oligoarthritis and degenerative cranial cruciate ligament rupture. 1762 54

Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, prevents joint tissue injury in rats with adjuvant induced arthritis. Because activation of osteoclasts is central to the pathogenesis of bone erosion in patients with rheumatoid arthritis (RA), we investigated the influence of AjA on osteoclast differentiation and survival. Osteoclast cultures were established by stimulation of RAW264.7 cells and primary mouse bone marrow cultures with receptor activator of NF-kappaB ligand (RANKL). Simultaneous addition of AjA (15 and 30 microM) and RANKL to both culture systems significantly suppressed development of multinucleated osteoclasts (osteoclastogenesis) in a dose dependent manner, as determined by quantification of multinuclear, tartrate-resistant acid phosphatase (TRAP)-positive cells. AjA impaired growth of RAW264.7 monocytes and prevented further osteoclast formation in cultures in which osteoclastogenesis had already begun. Reduction by AjA of both monocyte growth and osteoclast formation was associated with apoptosis, assayed by annexin V and propidium iodide staining, and caspase activity. The anti-osteoclastogenic effects of AjA did not require the continuous presence of AjA in the cell cultures. Based on these findings, we propose that AjA or other nonpsychoactive synthetic analogs of Cannabis constituents may be useful therapy for diseases such as RA and osteoporosis in which bone resorption is a central feature.
 ...
PMID:Ajulemic acid, a nonpsychoactive cannabinoid acid, suppresses osteoclastogenesis in mononuclear precursor cells and induces apoptosis in mature osteoclast-like cells. 1778 50

Interleukin-1 receptor antagonist (IL-1Ra), is a natural blocker of the inflammatory cytokine interleukin-1. Using a rat adjuvant-induced arthritis (AIA) model of rheumatoid arthritis (RA), we examined the protective effects of IL-1Ra in bone metabolism in vivo after folate-mediated nonviral gene delivery. We detected secreted human IL-1Ra protein in serum and cultured primary osteoblasts of rats that were treated with chitosan-IL-1Ra and folate-IL-1Ra-chitosan nanoparticles, respectively. In vivo, IL-1Ra gene delivery significantly reverted alterations in bone turnover observed in arthritic animals by modulating the level of osteocalcin (OC) as well as the activities of alkaline phosphatase and tartrate-resistant acid phosphatase. The protective effects of these nanoparticles were evident from the decrease in the expression levels of interleukine-1beta and prostaglandin E(2) as well as osteoclast number and other histopathological findings. Compared to naked DNA and chitosan-DNA, folate-chitosan-DNA nanoparticles were less cytotoxic and enhanced IL-1Ra protein synthesis in vitro and offered a better protection against inflammation and abnormal bone metabolism in vivo. Nonviral gene therapy with folate-chitosan-DNA nanoparticles containing the IL-1 Ra gene seemed to protect against bone damage and inflammation in rat adjuvant-induced arthritis model.
 ...
PMID:Bone-protective effects of nonviral gene therapy with folate-chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis. 1850 Feb 47

The aim of the present study was to evaluate the changes in bone metabolism during the early phase of type II collagen-induced arthritis in rats and to evaluate whether a 10% dietary xylitol supplementation is able to protect against these changes. Arthritis was induced in female dark agouti rats by injections of type II homologous rat collagen emulsified with an equal volume of incomplete Freund adjuvant. In one group, the diet was supplemented with 10% xylitol. After 17 days, the rats were killed. Serum osteocalcin, as a marker of bone formation, and serum tartrate-resistant acid phosphatase, as a marker of bone resorption, were measured. Histologic measurements were made from Masson-Goldner trichrome-stained sections of distal tibiae. All the collagen-injected rats had arthritic symptoms at the end of the experiment. Serum osteocalcin was significantly higher in the collagen-injected rats fed a xylitol-supplemented diet (CI-X) than in the collagen-injected rats not fed xylitol (CI) and in the controls. Serum tartrate-resistant acid phosphatase was significantly higher in the CI and CI-X groups than in the controls. Trabecular bone volume was significantly lower in the CI group as compared with the CI-X and control groups. These results suggest that, at the time of the appearance of arthritic symptoms, bone resorption activity is high, but bone formation is not severely affected. Furthermore, dietary xylitol seems to protect against the imbalance of bone metabolism during the early phase of collagen type II-induced arthritis.
 ...
PMID:Dietary xylitol protects against the imbalance in bone metabolism during the early phase of collagen type II-induced arthritis in dark agouti rats. 1864 Mar 81


<< Previous 1 2 3 4 5 6 7 8 Next >>