Twenty-five dogs were included in a randomized, double-blind trial to assess the efficacy of doxycycline (DOX) orally administered twice a day at 4 mg/kg/day (n = 12) for the treatment of osteoarthritis of the hip. Chondroitin sulfate (CS; 525 mg/day) was used as a positive control (n = 13). Dogs were re-examined monthly for 6 months after initiation of treatment. The assessment protocol included clinical score, radiographic findings and serum osteoarthritis biomarkers. Dogs treated with DOX showed statistically significant improvements (p < 0.05) in lameness, joint mobility, pain on palpation, weight-bearing and overall score at 2, 6, 4, 4 and 4 months, respectively, after treatment. Biomarker levels of CS-WF6 epitope and hyaluronan were significantly increased and decreased (p < 0.05) at 2 and 3 months after treatment compared to pretreatment. These results showed that DOX had a positive therapeutic effect in dogs with osteoarthritis.
Animals ; Biological Markers/blood ; Dog Diseases/*drug therapy ; Dogs ; Doxycycline/*therapeutic use ; Female ; Hyaluronic Acid/blood ; Joints/drug effects ; Lameness, Animal/drug therapy ; Male ; Osteoarthritis, Hip/drug therapy/*veterinary ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate the effect of alendronate on the prevention and treatment of aseptic loosening of prosthesis.

METHODSA rat model of particle-induced osteolysis was used. Thirty-xis SD rats were divided into three groups: negative control group, positive control group and experiment group. Alendronate was administered by ig in experiment group. Positive control group and experiment group received intro-articular injections of ultrahigh molecular weight polyethylene (UHMWPE) particles at 4, 6, 8, 10 weeks postoperatively. Negative control group was received injection with mixture solution of mouse serum and PBS only. All animals were sacrificed at 12 weeks after operation for histologic examination. In vitro human peripheral blood mononuclear (PBMC)were separated and cultured and divided into five groups as group A: PBMC group, group B: PBMC and particles,group C:PBMC and particles with 10(-4) mol/L alendronate, group D:PBMC and particles with 10(-5) mol/L alendronate, group E: PBMC and particles with 10(-6) mol/L alendronate. The production of IL-1beta, IL-6, TNF-alpha in each group were tested.

RESULTSAlendronate could prevent particle-induced osteolysis. The production of IL-1beta, IL-6, TNF-alpha was inhibited when alendronate was used.

CONCLUSIONAlendronate can inhibit bone absorptive factors expression induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis.

Alendronate ; administration & dosage ; Animals ; Cytokines ; metabolism ; Female ; Humans ; Joint Prosthesis ; adverse effects ; Joints ; metabolism ; surgery ; Male ; Osteolysis ; drug therapy ; metabolism ; prevention & control ; Prosthesis Failure ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study on the method of combining rhBMP(2) with porous-coated implants, and compared the histological and biomechanical results of 4 types of implants by being inserted into the femur of canine.

METHODS4 types of implants which are porous-coated implants (PCA), PCA implants combined with BMP, PCA implants coated with hydroxyapatite and HA coated cylindrical implants had been inserted into the femur of 16 canines. After 4, 8, 12 and 24 weeks the femur of the canines with the implants were retrieved. Bone ingrowth and shear strength of the interface was studied and analysed by the means of X-ray, soft X-ray, fluorescence tag, non-decalcification bone ground section, computer-aided image analysis procedure and biomechanical test.

RESULTSX-ray, soft X-ray, fluorescence tag, non-decalcification bone ground section and computer-aided image analysis procedure was used in histological study, and it showed that bony ingrowth into interface more than the other groups, even the maturation of newly formed bone. Non-decalcification bone ground section observation and computer aided image analysis showed the results: the new bone formation ratio of BMP group was 26.58% +/- 4.56% at 4 weeks post-implantation, which was much higher than the other groups, and there was significant difference between BMP group and each of the other group statistically (P < 0.05). Results of biomechanical study using push-out test showed that shear strength of each group appeared to rise with time. Shear strength of BMP group reached a high level at 4 weeks which was 18.94 +/- 5.11Mpa and almost twice of the other group, and there was also statistical difference between BMP group and each of the other group (P < 0.05). And the new bone formation ratio and shear strength of BMP group at 8, 12, 24 weeks post-implantation was still higher than the other group, but there was no statistically difference.

CONCLUSIONSPorous-coated implants combined with rhBMP can enhance bone ingrowth at bone-implant interface especially at the early period post-implantation. Porous-coated implants combined with rhBMP(2) can not only shorten the time of new bone formation and bone ingrowth but also enhance shear strength of bone-implant interface.

Animal Experimentation ; Animals ; Arthroplasty, Replacement ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; pharmacology ; Dogs ; Female ; Implants, Experimental ; Joints ; drug effects ; surgery ; Male ; Osteogenesis ; drug effects ; Time Factors ; Transforming Growth Factor beta

OBJECTIVETo investigate the efficacy of Qigui Tongfengshu granule in treating gouty arthritis.

METHODQigui Tongfengshu granule was used to treat 16 patients with gouty arthritis for 14 d.

RESULTThe recovery rate, marked effective rate, effective rate and improvement rate were 37.5%, 50%, 6.25%, 6.25%, respectively. The total effective rate was 100%. Before and after treatment, the comparison showed statistical significance.

CONCLUSIONQigui Tongfengshu granule is significantly effective for gouty arthritis, and has the effect of anti-inflammation, analgesia and reduction in blood uric acid.

Adult ; Aged ; Analgesia ; Anti-Inflammatory Agents ; administration & dosage ; Arthritis, Gouty ; blood ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Joints ; drug effects ; Male ; Middle Aged ; Pain Management ; Phytotherapy ; Treatment Outcome ; Uric Acid ; blood

OBJECTIVETo observe the effects of scorpion and centipede on interleukin (IL)-2, IL-4, IL-10 in the small intestinal mucosa and joint injury of rats with collagen induced arthritis (CIA).

METHODSSixty Wistar rats were randomly divided into 6 groups: the normal control group, the model group, the low dose scorpion and centipede group, the middle dose scorpion and centipede group, the high dose scorpion and centipede group, and the type II collagen treatment group. The joints' volume was measured 40 days after type II collagen (CII) induced rheumatoid arthritis model was established. The joint injury was observed by naked eyes. The expression levels of IL-2, IL-4, and IL-10 in the small intestine tissue homogenate were detected by enzyme linked immunosorbent assay (ELISA).

RESULTSThe joint injury score and volume of two hind limbs were obviously higher in the model group than in the normal control group since the 23rd day (P < 0.01). Rats were accompanied with red, swollen, and deformed foot toes and ankle joints. Walking was even affected. Meanwhile, the joint injury score and volume of two hind limbs were obviously lowered by medicated with 0.4, 0.2, 0.1 g/kg scorpion and centipede, as well as CII on the 32nd day after medication (P <0.05, P < 0.01). The expression levels of IL-2, IL-4, and IL-10 in the small intestine tissue homogenate were obviously lower in the model group than in the normal control group (P < 0.05, P < 0.01). Compared with the model group, only the expression levels of IL-2 and IL-4 in the small intestine tissue homogenate of the high dose scorpion and centipede group and the type II collagen treatment group significantly increased. The expression level of IL-10 significantly increased in the high and middle dose scorpion and centipede groups, as well as the type II collagen treatment group, showing statistical difference (P < 0.05, P < 0.01).

CONCLUSIONSScorpion and centipede could effectively release the joint injury of rats with CIA. Its mechanism might be correlated with increased expression levels of IL-2, IL-4, and IL-10 in the small intestine mucosa.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Intestinal Mucosa ; drug effects ; metabolism ; Intestine, Small ; metabolism ; Joints ; metabolism ; pathology ; Rats ; Rats, Wistar ; Scorpions

OBJECTIVETo investigate the anti-inflammatory, antioxidant and anti-arthritic effects of Centella asiatica methanolfraction (CaME) on collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis.

METHODSArthritis was induced in female wistar rats by immunization with porcine type II collagen. The CIA rats were treated orally with CaME (50, 150, and 250 mg/kg/day) for 15 d (beginning on day 21 of the experimental period). The clinical, histological, biochemical, and immunological parameters were assessed.

RESULTSCaME treatment (150 and 250 mg/kg) significantly attenuated the severity of CIA and reduced the synovial inflammation, cartilage erosion, and bone erosion as evident from both histological and radiographic data. The escalated plasma levels of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-12 alongwith nitric oxide in CIA rats decreased significantly on CaME treatment. The serum levels of type-II collagen antibody were significantly lower in rats of CaME (150 and 250 mg/kg) treated group than those in the arthritic group. Furthermore, by inhibiting the above mediators, CaME also contributed towards the reversal of the disturbed antioxidant levels and peroxidative damage.

CONCLUSIONOur results clearly indicate that oral administration of CaME suppresses joint inflammation, cytokine expression as well as antioxidant imbalance, thereby contributing to an amelioration of arthritis severity in CIA rats.

Animals ; Arthritis, Experimental ; blood ; drug therapy ; Centella ; chemistry ; Cytokines ; metabolism ; Drug Evaluation, Preclinical ; Female ; Flavonoids ; analysis ; Free Radical Scavengers ; analysis ; Free Radicals ; metabolism ; Joints ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; metabolism ; Nitric Oxide ; metabolism ; Oxidative Stress ; drug effects ; Phenols ; analysis ; Phytotherapy ; Proanthocyanidins ; analysis ; Random Allocation ; Rats, Wistar ; Triterpenes ; pharmacology ; therapeutic use

OBJECTIVETo observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats.

METHODSSixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1β, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction.

RESULTSMTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05).

CONCLUSIONSNCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.

Animals ; Arthritis, Experimental ; blood ; drug therapy ; pathology ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; therapeutic use ; Cytokines ; blood ; Forkhead Transcription Factors ; metabolism ; Joints ; drug effects ; pathology ; Male ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1beta regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1beta, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1beta to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1beta each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1beta did not synergistically support the degradation of IkappaB-alpha or the nuclear translocation of NF-kappaB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-kappaB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1beta may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.
Adiponectin/administration & dosage/*metabolism ; *Arthritis, Rheumatoid/metabolism/pathology ; Cells, Cultured ; Cyclooxygenase 2/metabolism ; Gene Expression Regulation/drug effects ; Humans ; *Inflammation/metabolism/pathology ; Interleukin-1beta/administration & dosage/*metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Joints/metabolism/pathology ; Matrix Metalloproteinases ; NF-kappa B/metabolism ; Obesity/metabolism/pathology ; Osteoarthritis ; Receptors, Adiponectin/metabolism ; Receptors, Interleukin-1/metabolism ; *Synovial Fluid/cytology/metabolism