Pannus Formation (pannu + formation)

Distribution by Scientific Domains


Selected Abstracts


Analysing the effect of novel therapies on cytokine expression in experimental arthritis

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2005
Richard O. Williams
Summary Type II collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Pro-inflammatory cytokines, such as tumour necrosis factor , and interleukin-1,, are expressed in the arthritic joints in both murine CIA and human rheumatoid arthritis, and blockade of these molecules results in amelioration of disease. Hence, there is a great deal of interest in the development of small-molecular-weight inhibitors of pro-inflammatory cytokines. There is also interest in the development and testing of drugs with the capacity to modulate the immune pathways involved in driving the inflammatory response in arthritis. For these reasons, there is a need to monitor the effect of novel treatments on cytokine expression in vivo. In this review, we outline the various techniques used to detect cytokines in experimental arthritis and describe how these techniques have been used to quantify changes in cytokine expression following therapeutic intervention. [source]


Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment

ARTHRITIS & RHEUMATISM, Issue 10 2009
S. Bar-Yehuda
Objective Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A3 adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. Methods OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 ,g/kg given twice daily) was initiated. The A3 adenosine receptor antagonist MRS1220 (100 ,g/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O,fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. Results CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-,B signaling pathway, resulting in down-regulation of tumor necrosis factor ,. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. Conclusion CF101 deregulated the NF-,B signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA. [source]


Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice

ARTHRITIS & RHEUMATISM, Issue 2 2009
Lies Geboes
Objective To investigate the role of interleukin-22 (IL-22) in collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. Methods C57BL/6 mice were immunized with type II collagen (CII) in Freund's incomplete adjuvant with added Mycobacterium tuberculosis, and levels of IL-22 and its specific receptor, IL-22 receptor type I (IL-22RI), were measured in sera and tissue by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction analysis. Clinical and histologic signs of arthritis were recorded and compared with those in C57BL/6 mice deficient in the IL-22 gene (IL-22,/,). Humoral and cellular immune responses against CII were analyzed. In vitro osteoclastogenesis assays were performed on splenocytes. Results Upon immunization with CII in Freund's incomplete adjuvant plus heat-killed Mycobacterium tuberculosis, sera from C57BL/6 mice were found to contain high levels of IL-22, and the specific IL-22RI was expressed in lymphoid tissue, including splenocytes. IL-22,/, mice were less susceptible to CIA than were wild-type mice, as evidenced by their decreased incidence of arthritis and decreased pannus formation. Remarkably, the less severe form of arthritis in IL-22,/, mice was associated with increased production of CII-specific and total IgG antibodies, whereas cellular CII responses were unchanged. In vitro, IL-22 was found to promote osteoclastogenesis, a process that might contribute to its proinflammatory activity in CIA. Conclusion Endogenous IL-22 plays a proinflammatory role in CIA in C57BL/6 mice. Our data also indicate that IL-22 promotes osteoclastogenesis and regulates antibody production. [source]


Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts

ARTHRITIS & RHEUMATISM, Issue 12 2007
Masako Seki
Objective To compare the expression of galectin 9 (Gal-9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these patients. Methods The expression of Gal-9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G1 method in vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis (CIA) in a mouse model were also elucidated. Results The percentage of Gal-9,positive cells in ST samples and the amount of Gal-9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal-9 in the development of RA. Compared with the 2 wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal-9,treated mice, but not phosphate buffered saline,treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction. Conclusion Gal-9,induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA. [source]


Histopathologic changes at "synovio,entheseal complexes" suggesting a novel mechanism for synovitis in osteoarthritis and spondylarthritis

ARTHRITIS & RHEUMATISM, Issue 11 2007
Michael Benjamin
Objective To determine the extent to which different entheses form part of a "synovio,entheseal complex" (SEC) and whether such SECs are commonly associated with the presence of inflammatory cells and evidence of enthesis microdamage. Methods Specimens from 49 cadaveric entheses were processed for histologic study, and all soft tissue components of the entheses or enthesis organs were examined. To exclude articular cartilage degeneration as a triggering factor for synovitis, the selected entheses included 17 that were not immediately adjacent to such cartilage. Results An SEC was present at 82% of entheses. These included 47% of the attachments not adjacent to articular cartilage, where the synovium was that of bursae or tendon sheaths. One or more of a wide variety of degenerative changes were noted on the soft tissue side of every enthesis; the most common changes were cell clustering and/or fissuring (in 76% of entheses). Synovial villus formation or inflammatory cell infiltration was seen in 85% of entheses, and in 73% of attachments there were also inflammatory cells in the enthesis organ itself. The changes included synovial invasion (pannus formation) of the enthesis. Conclusion Entheses are frequently juxtaposed to synovium, thus forming SECs. They are also often associated with both degenerative and inflammatory changes, and the latter may involve the immediately adjacent synovium. These findings suggest a novel mechanism by which synovitis could develop in both degenerative joint disease and spondylarthritis. [source]


Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor ,

ARTHRITIS & RHEUMATISM, Issue 9 2006
Carl K. Edwards III
Objective The roles of the transmembrane and secreted forms of tumor necrosis factor , (TNF,) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNF, have shown varying efficacy in RA patients, suggesting that anti-TNF, agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNF,) and secreted TNF,. In this study, TNF,-knockout (TNF,-KO) mice that were genetically altered to express elevated levels of tmTNF, were constructed to further understand the roles of the 17-kd secreted, trimeric, and 26-kd transmembrane forms of TNF,. Methods A speed-congenic mating scheme was used to generate 3 unique strains of mice: 1) transgenic tmTgA86 mice overexpressing 26-kd tmTNF, and also secreting 17-kd trimeric TNF, (tmTNF,-transgenic), 2) TNF,,/, mice (TNF,-KO), and 3) transgenic mice overexpressing tmTNF, backcrossed to TNF,-KO mice (tmTNF,-transgenic/TNF,-KO). Mice were treated with phosphate buffered saline (as vehicle control), dexamethasone (as positive control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75, and were assessed clinically and histopathologically for signs of inflammation and development of arthritis. Results The tmTNF,-transgenic/TNF,-KO mice were born with crinkled tails and spinal deformities similar to those in ankylosing spondylitis. By 2,4 weeks, these mice developed symmetric inflammatory arthritis, characterized by tissue swelling, pannus formation, and bone deformities. The tmTNF,-transgenic mice also developed spontaneous-onset arthritis, but at a slower rate (100% incidence by 10,12 weeks). Clinical and histologic progression of arthritis in the tmTNF,-transgenic/TNF,-KO mice was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and 63% reduction in total histologic score, respectively). Conclusion These data show that arthritis is sufficiently initiated and maintained in tmTNF,-transgenic/TNF,-KO mice, and that it can be neutralized by recombinant human p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent histologic destructive effects of tmTNF,. [source]


Enhancement of the anti-inflammatory and anti-arthritic effects of theophylline by a low dose of a nitric oxide donor or non-specific nitric oxide synthase inhibitor

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2009
Adel Gomaa
Background and purpose:, Although there are many new specific phosphodiesterase inhibitors with anti-inflammatory activity, none have yet reached the market because of their low therapeutic efficacy. Our study was aimed to evaluate the anti-inflammatory and anti-arthritic effect of an established phosphodiesterase inhibitor, theophylline, and to investigate the effect of the nitric oxide (NO) donor, sodium nitroprusside (SNP) or NO synthase inhibitor, L-NG -monomethyl arginine (L-NMMA) on its actions. Experimental approach:, The effects of theophylline alone and combined with SNP or L-NMMA on the pathogenesis of adjuvant-induced arthritis in rats were evaluated. Key results:, Prophylactic or therapeutic doses of theophylline significantly ameliorated the pathogenesis of adjuvant arthritis in rats as evidenced by a significant decrease in the arthritis index, hind paws volume, ankle joint diameter, fever, body weight loss and hyperalgesia in a dose-dependent manner. Inflammatory cellular infiltrate in synovium of ankle joint and pannus formation were also markedly inhibited. Interleukin-10 (IL-10) levels were significantly increased in arthritic rats given theophylline alone or in combination with either SNP or L-NMMA. Co-administration of a low dose of SNP or L-NMMA enhanced significantly the anti-inflammatory and anti-arthritic effect of theophylline. In contrast, a high dose of SNP counteracted the anti-inflammatory and anti-arthritic effects of theophylline. Conclusions and Implication:, These findings confirm the anti-inflammatory and anti-arthritic activities of theophylline and suggest a new approach to enhance the anti-inflammatory and anti-arthritic effects of theophylline would be to administer it in combination with a low dose of a NO donor or a non-specific NO synthase inhibitor. [source]