Arthritis In Rabbits Research Articles

Effect of methotrexate on the mandibular development of arthritic rabbits

Juvenile idiopathic arthritis affecting the temporomandibular joint (TMJ) can cause severe disturbances of the mandibular development. Methotrexate (MTX) is often administered as a common used remission-inducing agent to treat this disease. The aim of this study was to investigate the effect of low dose MTX on the mandibular growth in arthritic rabbits. Eighteen 10-week-old female New Zealand white rabbits were randomly assigned to three groups with six animals in each group. After being sensitized to ovalbumin (OA), the first and the second group received intra-articular injections with OA. The first group remained untreated, the second was treated by weekly injections of MTX. Cephalograms were taken from each animal at 10, 13, 16, 19, and 22 weeks of age and six mandibular distances measured. All distances showed an increase between 10 and 20 per cent, whereas growth was more accentuated in the sagittal dimension. Significant differences in the overall growth could be observed between the arthritic and the control animals and less accentuated between the arthritic and the MTX animals. In contrast, existing differences between the groups were not significant during the intervals, but time had the greatest influence on mandibular growth. MTX seems to have a positive impact on growth in rabbits suffering from experimental arthritis of the TMJ.

Tolerancia oral en artritis experimental inducida por antígeno en conejos por administración de hidrolizado de cartílago articular

Rheumatoid arthritis is an autoimmune disease characterized by polyarticular inflammation, swelling and inflammation that affects more than 1% of the world population. The pathobiology of rheumatoid arthritis involves several cell populations as T lymphocytes, B, macrófagosy fibroblasts, and a complex proinflammatory cytokines interactions. Conventional and biologic therapies do not always work or produce only a partial improvement. Immunological tolerance is a mechanism by which the immune system prevents autoreactivity. The aim of this pilot study was to evaluate the efficacy of peptides from an from articular cartilage hydrolysate extracted of tarsus (HCA) for the treatment of rheumatoid arthritis in a model of rheumatoid arthritis (AAE) in rabbits. AAE animals showed inflammation and pain within de first month of the primary immunization that was reversed in the AAE + HCA group. The control group showed a normal unnaffected synovial tissue. The AAE group revealed an inflamatory process whith synovial hyperplasia, filtering in lymphocytes and vascular proliferation. The treated group decreased significantly inflammation, lymphocyte proliferation and angiogenesis. Arthritic rabbits increased the levels in flammatory markers as nitric oxide, interferon gamma (INF-ɣ) and tumor necrosis factor alpha (TNF-α) compared to control and significantly reduced levels of interleukin 4 (IL-4). The treatment showed a significant reduction of nitricoxide, IFN-gamma and TNF-alpha and an increase in IL-4. This work suggests that this therapy may be useful in the clinical aspect and the biochemical and immune parameters. Future studies with larger numbers of animals and other laboratory parameters may provide additional evidence in this regard.

Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.

Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.

Anti-Inflammatory Effects of Vitis thunbergii var. taiwaniana on Knee Damage Associated with Arthritis

Vitis thunbergii Sieb. et Zucc. var. taiwaniana Lu (VT) is an indigenous plant in Taiwan that is traditionally used for promoting joint health. In this study, we used in vitro primary human chondrocytes (PHCs) and two in vivo animal models to evaluate the anti-inflammatory effects of VT on arthritis. Results showed that the water extract of the stems and roots from VT (VT-SR) was rich in flavones and phenols with 1.1 mg/g of resveratrol, 6.7 mg/g of hopeaphenol, and 5.1 mg/g of (+)-ɛ-viniferin. VT-SR significantly scavenged DPPH radicals and inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-induced PHCs without exhibiting significant cytotoxicity. In in vivo models, the VT-SR (500 mg/kg) significantly decreased serum PGE2 and knee 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) levels in LPS-induced acute inflammatory arthritis in rabbits. In addition, dietary supplementation with VT-SR for 28 days significantly alleviated type II collagenase-induced rat osteoarthritis with improvements in weight bearing and range of motion tests. In conclusion, our results suggest that the VT-SR is a good candidate for developing dietary supplements to prevent joint deterioration and inhibit inflammation.

Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis

To explore the characteristic expression of endoplasmic reticulum (ER) stress protein in antigen-induced arthritis models and the role of ER stress in arthritis. Effective animal models of rheumatoid arthritis in rabbits and rats were induced by methylated bovine serum albumin and Freund's complete adjuvant. Pathological changes were assessed by magnetic resonance imaging and histological analysis. The expression and localization of ER stress proteins in synovium and peritoneal macrophages (PMΦ) were analyzed by double immunofluorescence staining. RT-PCR was performed to detect mRNA expression of ER stress-related genes. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in synoviocytes were measured by RT-PCR and radioimmunoassay. We found that the ER stress marker BiP was highly up-regulated in arthritis synovium and extensively expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS). The expression of the pro-apoptotic factor CHOP/GADD153 was slightly elevated in inflammatory synovium and mainly localized in FLS, but insignificant in MLS. Unexpectedly, increased expression of CHOP was observed in PMΦ in arthritis rats. Likewise, cleaved caspase-3 was rarely expressed in MLS. In addition, induction of ER stress by tunicamycin resulted in significantly increased expression of pro-inflammatory molecules such as IL-1β and TNF-α in cultured inflammatory FLS. Differential activation of the ER stress proteins in synovium MLS may contribute to the resistance of synoviocytes to ER stress-induced apoptosis. Furthermore, ER stress is a potential mediator of arthritis inflammation.

Early extremity MRI findings and pathological synovial changes in antigen-induced arthritis rabbit model

To investigate the association between early extremity MRI (E-MRI) findings and synovial pathological changes in antigen-induced arthritis (AIA) rabbit model. AIA was successfully induced in the right knee of 32 sensitized Japanese white rabbits, which were then divided into four groups according to the time of killing after AIA induction: 1-week (Group A), 2-weeks (Group B), 3-weeks (Group C), and 4-weeks (Group D); the left knee served as control in each rabbit. There were varying degrees of joint effusion in all AIA groups. E-MRI scan showed low signal in T1-weighted images (T1Wi) and high signal in T2-weighted images (T2Wi). Enhanced E-MRI revealed elevated synovial signal at the right knee in the three-dimensional spoiled gradient T1WI, showing linear and band-shaped, diffuse hyperintensity. Histological examination of right knees found scattered inflammatory cell infiltration, swelling, and proliferation of the synovial cells at 7 days after AIA induction and dispersed and disordered proliferation of synovial cells up to 3 layers at 28 days postinduction. The synovial enhancement of right knee E-MRI was consistent with a synovial pathology score for all rabbits (Kappa = 0.965, P < 0.01). E-MRI can reveal the degree of changes in the joints and synovium at different periods of the AIA model.

Spectroscopic assessment of endogenous porphyrins in a rheumatoid arthritis rabbit model after the application of ALA and ALA-Me

The sensitization of inflamed knee tissues with endogenous porphyrins was studied by means of fluorescence spectroscopy in an experimental model of rabbit rheumatoid monoarthritis after intraarticular (i.a.) or intravenous (i.v.) injections of 5-aminolevulinic acid (ALA) or ALA methyl ester (ALA-Me). Fluorescence measurements in vivo on the skin of the inflamed knee joint showed the dominance of protoporphyrin IX (PpIX). The highest fluorescence intensity was registered 2h after i.a. injection of ALA and ALA-Me. Comparative analysis of the PpIX fluorescence spectra ex vivo revealed that more PpIX accumulated in the tissues of the inflamed joint than in the tissues of the control joint, and that ALA-Me induced about five times more PpIX in the inflamed synovium than ALA. Meanwhile, the cartilages of the inflamed and control knee joints also accumulated water-soluble porphyrins. Thus, in vivo and ex vivo spectroscopic assessment of endogenous porphyrins in rabbit rheumatoid arthritis tissues implied that the injection of ALA is more appropriate for the diagnostics of inflammation due to the higher PpIX fluorescence intensity on the skin surface, while ALA-Me is more appropriate for the therapeutic applications due to the higher and more selective accumulation of PpIX in the inflamed synovium.

Study the influence of whole sonicated Staphylococcus aureus antigens on septic arthritis in rabbits infected with these microorganism

In order to know the influence of whole sonicated S.aureus antigens (WSSAgs) on S.aureus septic arthritis, 15, white local rabbits, both sex, their weights ranged between 1.25-1.50 Kg ,were randomly divided into 3 equal groups and treated as follow:1-the 1ST group was immunized with 0.5 ml of WSSAgs (3.3mg/ml protein concentration), two doses,14 days interval, at 28 days post-immunized .skin test was done by used soluble sonicatated S. aureus antigens and at day 30,Ab titers was recorded ,then the Vt and 2nd groups were challenged with 0.5ml of bacterial suspension containing 1X1OCFU/ml ,intra -synovial. the 3 group was inoculated with 0.5 ml of sterile normal saline and served as control negative group. All animals were sacrificed at 30 days post- challenge, sample from knee joint were taken for bacterial isolation and pathological examination. The results showed that WSSAgs elicited both humoral and cellular immune responses against S.aureus infection .severe swelling of the knee joint was noticed in the 2 group as well as the animals unable to use their legs. heavy bacterial isolation from infected joints was recorded in the 2nd group with severe histopathological lesions in the infected joints characterized by suppurative inflammation of the perchondral area with inflammatory reaction, necrosis and erosion of the articular cartilage and these changes were extended to subchondral bone trabeculae and bone marrow lead to suppurative inflammaion and necrosis of the bone trabeculae .while there was no clinical signs and no bacterial isolation reported in immunized infected animals as well as no clear pathological changes t noticed in joints of immunized-infected animals.

RANKL produced by articular chondrocytes contributes to juxta-articular bone loss in chronic arthritis

Background and objetivesJuxta-articular bone loss is an early lesion of rheumatoid arthritis (RA) whose molecular mechanisms are still unknown. Although the authors have previously demonstrated that RANKL diffuses from cartilage...

Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

EXPERIMENTAL STUDY FOR EVALUATION OF ANTIMICROBIAL ACTIVITY OF THE AQUEOUS GARLIC EXTRACT IN TREATMENT OF ARTHRITIS IN RABBITS

The study was conducted to evaluate the ability of Aqueous Garlic Extract (AGE) for inhibition the growth of Salmonella typhimurium as a probable cause of arthritis in rabbits in vitro and in vivo study. Results revealed that AGE (contain 201.2µg/ml allicin) have excellent antibacterial activity against this strain at ≥60% concentration, while the concentration ≥20% showed moderate activity, M oreover concentration of <20% show no effect in vitro. The in vivo study was explained the infectious dose of Salmonella typhimurium that induce arthritis in experimental animals was ≥ 1×105 C.F.U/ml when injected intrarticularly. Garlic extract was administrated to treat experimental induced arthritis for 5 days by using different doses subcutaneously. It have been shown that a dose rate of 100mg/kg B.W S.C were more effective and have no adverse effects. Some bacteriology, serology and hematological tests were used as indicators to confirm infection and evaluation of treatment in rabbits.

Expression of Survivin, CD117, and C-erbB-2 in Neuroendocrine Carcinoma of the Uterine Cervix

To evaluate the expression and prognostic significance of survivin, CD117, and C-erbB-2 in neuroendocrine carcinoma of the uterine cervix. Immunohistochemical stains of survivin, CD117, and C-erbB-2 were evaluated in 100 cases of cervical neuroendocrine carcinoma. The findings were correlated with clinicopathologic variables and disease-free survival. Expressions of survivin, CD117, and C-erbB-2 were detected in 27.0%, 12.0%, and 2.0% of the cases, respectively. Survivin-positive patients had a significantly younger mean age than the survivin-negative group (P=0.033). In early-stage cases, tumor recurrence was significantly associated with lymph node metastasis (P=0.005), depth of invasion (P=0.028), and the presence of lymphovascular space invasion (P=0.031) but not with the expression of survivin or CD117. Subgroup analysis in early-stage cases without lymph node metastasis (n=32) showed that only survivin expression had a significant association with decreased disease-free survival (P=0.041). Survivin expression may be a prognostic indicator for survival in early-stage neuroendocrine carcinoma of the uterine cervix without lymph node metastasis. Adjuvant survivin-targeted therapy may have potential benefit in patients with this tumor.

Retention and distribution of liposome-entrapped [3H]methotrexate injected into normal or arthritic rabbit joints.

Normal or arthritic rabbits were injected intra-articularly (i.a.) with free [3H]methotrexate ([3H]MTX) or liposomes containing [3H]MTX with [14C]cholesteryl oleate as a lipid marker. The distribution of 3H and 14C in the injected joint and other tissues was determined. Free [3H]MTX was rapidly cleared from the joint, 79% being excreted in the urine within 24 h of injection. Liposome-entrapment retarded [3H]MTX clearance from the joint (P less than 0.001), 45.5% being recovered from the joint 24 h after injection. Uptake of liposomes by the inflamed synovium was lower than expected, 4% liposomal [3H]MTX injected being associated with the synovium after 24 h. Nevertheless, this was 40-fold greater than when free [3H]MTX was injected. Liposome entrapment should improve the efficacy and reduce the side effects of drugs injected directly into the joint cavity.

Reliability and Convergent Validity of Different BOLD MRI Frameworks for Data Acquisition in Experimental Arthritis

The clinimetric properties of blood oxygen level‒dependent (BOLD) magnetic resonance imaging (MRI) for assessment of musculoskeletal changes have been poorly investigated. The study objectives were to assess the interframework reliability of data acquisition of BOLD MRI and to test its convergent validity in chronic arthritis in a rabbit model of inflammatory arthritis as compared with corresponding clinical and laboratory measures. One of the knees of 12 New Zealand male white rabbits was injected with a 1% carrageenin solution, and the contralateral (control) one was not. Twelve rabbits were euthanized on day 28 of arthritis (chronic arthritis). Clinical (joint diameters), laboratory (serum amyloid A concentration), and BOLD MRI measurements were obtained on days 0, 1, and 28 of arthritis. Twenty paradigms of data acquisition and analysis were applied. The most reliable MRI parameters set, regardless of threshold values used for data analysis, was spiral technique (level 1), 40 ms of echo time (level 2), 60 seconds of on_ and off_ paradigm (level 3) and carbogen mixture of gases (95% O2 + 5% CO2) (level 4). With regard to construct validity, BOLD imaging correlated moderately (r = -.54, P < .0001) with knee diameters, and weakly (r = -.35, P = .01) with laboratory indices (high threshold for analysis). BOLD MRI has a substantial or excellent interframework reliability for assessment of arthritic rabbit knees; however, it correlates only moderately or poorly with clinical and laboratory measures. Nevertheless, this study supports further validation of BOLD MRI for assessment of soft tissue changes in a rabbit model of arthritis.

Antigen-induced arthritis in rabbits: a comparative study between high-resolution ultrasound and contrast-enhanced ultrasound and pathologic findings

The objective of this study was to explore the feasibility and value of high-resolution ultrasound and contrast-enhanced ultrasound in evaluation of synovitis in rabbit knee joint in antigen-induced arthritis (AIA). Thirty-six rabbits were divided into three groups, each injected with different doses of ovalbumin (OVA) into the right knee joint. On week 1 and 4, 6 randomly selected in each group were killed. Each knee joint undergone the high-resolution ultrasound to measure capsule thickness and contrast-enhanced ultrasound to measure synovium thickness. The results from the ultrasound examinations were compared with those of pathologic examinations. Different OVA doses resulted in different modeling success rate, different pathological synovitis score, and different capsule and synovium thickness measured by ultrasound. The diagnostic accuracy of synovitis by ultrasound was high. The ultrasound measurement revealed that the capsule thickness on week 4 was lessened than that on week 1, while the synovial thickness on week 4 was greater than that on week 1. Both the joint capsule and synovium thickness measured by ultrasound were significantly and positively correlated to the pathologic synovitis score (P<0.05). The synovial thickness on week 4 is more correlated to the synovitis score than the capsule thickness, rather than that on week 1. Injection of OVA of different doses results in different modeling success rate and synovitis severity. The high-resolution ultrasound and contrast-enhanced ultrasound can be used to determine whether the AIA was made successfully and evaluate the synovitis severity. In chronic inflammatory phase, the contrast-enhanced ultrasound has better effect.

Noninvasive Quantitative Assessment of Synovial Pannus Angiogenesis by Contrast-enhanced Gray-scale Sonography in Antigen-induced Arthritis in Rabbits

The aim of this study was to evaluate the value of contrast-enhanced gray-scale sonography in quantitative assessment of synovial pannus angiogenesis in antigen-induced arthritis in rabbits. Twenty-four adult New Zealand White rabbits were divided into two groups. Inflammatory arthritis was induced by intra-articular injection of ovalbumin into right knee joints with 4 mg in low-dose group (LD, n = 12) and 8 mg in high-dose group (HD, n = 12). The left side of the knee on each rabbit was used as normal control. Contrast-enhanced gray-scale sonography with time intensity curve (TIC) was performed on the synovia of suprapatellar bursa and posterior capsules 4 weeks after the injection. Immunohistochemical examinations of synovia were applied to assess the microvessel density and the expression of vascular endothelial growth factor. Correlation analysis between sonographic and immunohistochemical findings was performed. Contrast-enhanced gray-scale sonography of all right knees demonstrated intra-articular hypoechoic lesions with enhanced blood flow and no abnormal findings on all left knees. Parameters of TIC, including ascending curve (A), derived peak intensity (DPI), and area under curve (AUC) on arthritis joints were significantly higher in HD group compared to LD group (P < .05). Positive correlation was found between immunohistochemical findings and parameters of A, DPI, and AUC (P < .05). However, no correlation was found between other parameters (slope of descending rate, time to peak, time to rise, and initial intensity) and immunohistochemical findings. Contrast-enhanced gray-scale sonography with TIC measurement could provide reliable method for noninvasive quantitative assessment of synovial pannus angiogenesis of arthritis in clinical settings.

Simultaneous Dual Frequency $^{1}{\rm H}$ and $^{19}{\rm F}$ Open Coil Imaging of Arthritic Rabbit Knee at 3T

The combination of sensitive magnetic resonance techniques with a selective site-targeted nanoparticle contrast agent has a demonstrated utility for molecular imaging studies. By detecting a unique signature of the contrast agent, this approach can be employed to identify specific bio-molecular markers and observe cellular-level processes within a large and complex organism (e.g., in vivo rabbit). The objective of the present investigation was to design, fabricate and characterize a radio-frequency (RF) coil for the dual frequency ((1)H and (19)F) simultaneous collection of both nuclei images in a 3T field, in order to facilitate studies of arthritic knee degradation in rabbits. The coil supports both transmit and receive modes. The supporting activities included: 1) establishing a technical database for calculating the required coil parameters, 2) selection of a favorable coil geometry, and 3) adaption of existing RF measurement techniques to the design, development and electrical evaluation of the coil. The coil is used in conjunction with a Philips Medical Systems clinical MRI scanner, requiring all RF simultaneous dual frequency ((1)H and (19)F) coils to operate in both transmit and receive modes. A commercial version of SPICE (simulation program with integrated circuit emphasis) was used to estimate significant operational parameters prior to fabricating the imaging coil. Excellent images were obtained with the fabricated coil and no operational problems were observed that would limit the use of other coil geometries and field strengths.

Anti-inflammatory effect of bee venom on antigen-induced arthritis in rabbits: Influence of endogenous glucocorticoids

Aim of the study This study assessed the involvement of endogenous glucocorticoids (GCs) in the anti-arthritic properties of bee venom (BV) on antigen-induced arthritis (AIA) in rabbits. Materials and methods BV (1.5–6 μg/kg/day) was injected for 7 days before AIA induction, whereas the control group received sterile saline. The total and differential leukocyte count, PGE 2 levels in synovial fluid and synovial membrane cell infiltrate were evaluated. The contribution of GCs to BV action was assessed in rabbits treated with BV plus metyrapone, an inhibitor of GC synthesis, or RU-38 486, a steroid antagonist. Results Treatment with BV (1.5 μg/kg/day) reduced the leukocyte count and PGE 2 level (18571 ± 1909 cells/mm 3 and 0.49 ± 0.05 ng/mL, respectively) as well as the cellular infiltrate compared with the control group (40968 ± 5248 cells/mm 3 and 2.92 ± 0.68 ng/mL, p < 0.05). The addition of metyrapone to BV treatment completely reversed the inhibition of AIA, whereas RU-38 486 was ineffective. Conclusion Our data show that bee venom treatment prevents the development of antigen-induced arthritis in rabbits through the action of GCs.

Establishment of a Experimental Antigen-induced Arthritis in Rabbit and Evaluation of its MRT Manifestations

Objective To establish a experimental rabbit model of antigen-induced arthritis and discuss its MRI manifestations.Methods Unilateral arthritis was induced by means of intraartieular injection of ovalbumin in 7 knees of 7 rabbits that had been presensitized to the same antigen.All knees were imaged at 5,15 days after onset of arthritis.MR findings were correlated with histopathologic findings.Results 6 knees with intraarticular injection of antigen suspension developed unilateral arthritis.Precontrast image showed thickening of joint effusion and synovium.The Joint effusion or synovium showed hypo-or/so-intensity on T1-weighted spin-echo,while inhomogeneouos hyper-intensity on T2-weighted spin-echo.It could be difficult to differentiated from one another.Postcontrast image (after Gd-DTPA administration) showed marked enhancement,whereas joint effusion did not.Synovium increasing was more distinctive on 15 day than on 5 day after intraarticular injection.The results of histopathologic evaluation confirmed the MR findings,with presence of marked to extensive synovial hyperplasia in all 6 arthritic knees of the antigen-injected group.Cellular infiltrates containing monocytes,lymphocytes,and macrophages were noted within the hyperplastic synovium of the arthritic knees.Conclusions The pathological process development and MRI manifestations in the rabbit model of antigen-induced arthritis is similar to that in human beings,so that it is a good lab model of rheumatoid arthritis. Key words: Experimental; Rabbit model of antigen-induced arthritis; MRI

Therapeutic effect of Aralia cordata extracts on cartilage protection in collagenase-induced inflammatory arthritis rabbit model

Aim of this study Aralia cordata has been used to alleviate symptoms of osteoarthritis (OA) in traditional medicine. However, there is no in vivo study related with the therapeutic effects and mechanisms of Aralia cordata. On the basis of this background, our study was designed to examine the cartilage protective and proliferative effects of Aralia cordata by using a collagenase-induced osteoarthritis (CIA) rabbit model. Materials and methods The right knees of rabbits were injected intra-articularly with collagenase, and rabbits were orally administered with distilled water (vehicle), Aralia cordata (200 mg/kg) and celecoxib (100 mg/kg) once a day for 28 days after the initiation of the CIA. Results In histopathologic studying by using H&E and Safranin O staining, Aralia cordata showed a cartilage protective effect in CIA rabbit femoral condyle. However, celecoxib had no effect on cartilage protection in CIA. The inflammatory mediators involved in cartilage destruction, such as COX-2 and PGE 2, were inhibited in the Aralia cordata-treated group. Aralia cordata also showed an anti-apoptotic effect through suppression of caspase-3 activity and chondrocyte proliferation induction in both in vivo and in vitro. Conclusion These results indicate that Aralia cordata showed cartilage protective effects through the down-regulations of COX-2 expression, PGE 2 production, caspase-3 activity, and chondrocyte proliferation in the CIA rabbit model.