Pathological Changes In Joints Research Articles

Immediate effects of varus bracing on knee mechanics in people with predominant lateral knee osteoarthritis and valgus malalignment, 12 years after anterior cruciate ligament reconstruction

Immediate effects of varus bracing on knee mechanics in people with predominant lateral knee osteoarthritis and valgus malalignment, 12 years after anterior cruciate ligament reconstruction

Bauhinia championii Extraction Treatment of Collagen-Induced Arthritis via Downregulation of the Expression of TLR4, MyD88 and NF-κB

Rheumatoid arthritis (RA) has emerged as an important worldwide public health problem. Due to the lack of efficacy and major side effects related to many Western medical treatments, traditional Chinese medicine or herbal medicine is very often used to treat this disease. In the present study, we evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) in a rat model of RA induced by type-II collagen. Wistar rats with type-II collagen-induced arthritis (CIA) were given either 125 or 500 mg/kg of BCBE for RA. Paw swelling and weight were measured, and pathological joint sections of CIA rats were observed using the hematoxylin and eosin (HE) staining method. Protein and mRNA expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor κB (NF-κB) were determined by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis in synovial tissue. During therapeutic treatment, BCBE significantly suppressed paw swelling, increased weight loss and ameliorated pathological joint changes. The protein and mRNA expressions of TLR4, MyD88 and NF-κB were downregulated in the CIA model when treated with BCBE. In conclusion, these results suggest that the treatment of RA with BCBE confers anti-RA activity and has therapeutic potential in this CIA model.

Evaluation of Verbascum species and harpagoside in models of acute and chronic inflammation

AbstractVerbascum species are widely used in folk medicine because of their broad range of biological activities. Harpagoside, an iridoid glycoside isolated from some Verbascum plants is known for its anti-inflammatory properties. In the present study, the effect of five extracts of Verbascum species and harpagosides were evaluated in mouse models of acute and chronic inflammation. The results demonstrate that Verbascum phoeniceum extract strongly inhibits COX-1 (60.2% inhibition vs PMA-stimulated cells) and COX-2 (44.8% inhibition) expression stimulated peritoneal macrophages resulting in reduced paw swelling in carrageenan-induced oedema (55.5% inhibition vs PBS-treated mice). Harpagoside ameliorated the development of zymosaninduced arthritis and reduced pathological changes in joints as shown by the decreased histological score for cell infiltration in synovial cavity (3.5±0.2 in vs 2.0±0.16), cartilage loss (2.5±0.3 vs 1.8±0.5) and bone resorption (2.4±0.2 vs 1.8±0.4). Molecular docking simulations of harpagoside suggest that it may function with increased specific affinity towards COX-1 than COX-2. The potential of harpagoside to be applied as an effective agent for treating joint-related disorders is discussed.

Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis for pharmacotherapy

Osteoarthritis (OA) of the knee and hip is among the most frequent and debilitating arthritic conditions. Aside from surgical intervention in severe cases, conventional treatment involves relieving painful symptoms with non-steroidal anti-inflammatory drugs (NSAIDs), narcotic and non-narcotic (weak) analgesics and physical therapy. To obtain insight into the extent of pathological changes in hip and knee OA we reviewed current literature on the pathogenesis of this state as a basis for current pharmacotherapy options. Key features of the pathological joint changes in OA include: cartilage destruction by pro-inflammatory cytokines, matrix metalloproteinases and prostaglandins, which promote a catabolic environment; subchondral bone remodelling and resorption; hypertrophic differentiation of chondrocytes; neovascularisation of synovial tissue; and focal calcification of joint cartilage. Despite the central involvement of hyaline cartilage in OA pathogenesis, the source of pain likely stems from the richly innervated synovium, subchondral bone and periosteum components of the joint. Tissue damage during joint degeneration generates nociceptive stimuli. The presence of inflammatory mediators, including bradykinin, prostaglandins and leukotrienes, lowers the threshold of the Aδ and C pain fibres, resulting in a heightened response to painful stimuli. It is our opinion that it is important to base and centre the management of OA patients on the severity of patient-important outcomes, rather than purely an assessment of damage to the joint. The joint damage, as interpreted from radiographs, is not necessarily representative of the symptoms experienced. The management of OA primarily comprises pharmacological therapy, surgical interventions and various non-pharmacological interventions.

Human umbilical cord mesenchymal stem cells as treatment of adjuvant rheumatoid arthritis in a rat model

To investigate the effect of human umbilical cord stem cells, both mesenchymal and hematopoietic (CD34+), in the treatment of arthritis. Mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells (HSC) were isolated from human umbilical cord blood obtained from the umbilical cord of healthy pregnant donors undergoing full-term normal vaginal delivery. MSC, HSC, methotrexate (MTX) and sterile saline were injected intra-articularly into the rat hindpaw with complete freunds adjuvant (CFA) induced arthritis after the onset of disease (day 34), when arthritis had become well established (arthritis score ≥ 2). Arthritic indices were evaluated and the levels of interleukin (IL)-1, tumor necrosis factor (TNF)-α and interferon (IFN)-γ and anti-inflammatory cytokine IL-10 in serum were determined using enzyme-linked immunosorbent assay. Animals of all groups were sacrificed 34 d after beginning treatment, except positive control (PC) which was sacrificed at 10, 21 and 34 d for microscopic observation of disease progression. We used hematoxylin, eosin and Masson's trichrome stains for histopathological examination of cartilage and synovium. The mean arthritis scores were similar in all groups at 12 and 34 d post immunization, with no statistical significant difference. Upon the injection of stem cells (hematopoietic and mesenchymal), the overall arthritis signs were significantly improved around 21 d after receiving the injection and totally disappeared at day 34 post treatment in MSC group. Mean hindpaw diameter (mm) in the MSC rats was about half that of the PC and MTX groups (P = 0.007 and P = 0.021, respectively) and 0.6 mm less than the HSC group (P = 0.047), as indicated by paw swelling. Associated with these findings, serum levels of TNF-α, IFN-γ and IL-1 decreased significantly in HSC and MSC groups compared to PC and MTX groups (P < 0.05), while the expression of IL-10 was increased. Histopathological examination with H and E stain revealed that the MTX treated group showed significant reduction of leucocytic infiltrate and hypertrophy of the synovial tissue with moderate obliteration of the joint cavity. Stem cells treated groups (both hematopoietic CD34+ and mesenchymal), showed significant reduction in leucocytic infiltrate and hypertrophy of the synovial tissue with mild obliteration of the joint cavity. With Masson's trichrome, stain sections from the PC group showed evidence of vascular edema of almost all vessels within the synovium in nearly all arthritic rats. Vacuoles were also visible in the outer vessel wall. The vessel became hemorrhagic and finally necrotic. In addition, there was extensive fibrosis completely obliterating the joint cavity. The mean color area percentage of collagen in this group was 0.324 ± 0.096, which was significantly increased when compared to the negative control group. The mean color area percentage of collagen in hematopoietic CD34+ and mesenchymal groups was 0.176 ± 0.0137 and 0.174 ± 0.0197 respectively, which showed a marked decrement compared to the PC group, denoting a mild increase in synovial tissue collagen fibers. MSC enhance the efficacy of CFA-induced arthritis treatment, most likely through the modulation of the expression of cytokines and amelioration of pathological changes in joints.

Treatment of collagen-induced arthritis with recombinant plasminogen-related protein B: a novel inhibitor of angiogenesis

BackgroundWe have previously reported that recombinant human plasminogen-related protein B (rPRP-B), a putative 9-kDa protein that closely resembles the activation peptide of plasminogen, has shown significant inhibition of tumor growth through inhibition of angiogenesis. Based on recent reports suggesting a close relationship between rheumatoid arthritis (RA) and angiogenesis, we hypothesized that this compound would regulate inflammatory conditions in RA. The present study therefore tested the effects of rPRP-B in the treatment of collagen-induced arthritis (CIA) to elucidate the mechanisms underlying these effects. MethodsDBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of rPRP-B on clinical severity of the disease. Pathological changes in joints, including vessel formation and vascular endothelial growth factor (VEGF) production, were examined histologically. Bone destruction was radiologically evaluated. In vitro studies on the effects of rPRP-B on cell proliferation and production of VEGF in interleukin (IL)-1β or basic fibroblast growth factor (bFGF)-stimulated human synoviocytes were also performed. ResultsDevelopment of CIA was effectively inhibited by rPRP-B. Radiological examinations revealed that the protein reduced bone destruction in CIA. CIA-induced vessel formation and VEGF expression in vivo were also reduced. In vitro mechanistic studies demonstrated that rPRP-B affected human synoviocyte proliferation and VEGF production stimulated by IL-1β and bFGF. ConclusionsGiven the ability to effectively promote multistep anti-angiogenic activities, including cell growth inhibition and cytokine regulation, rPRP-B represents a promising candidate for a novel therapeutic agent against RA.

Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate

A rat model of osteoarthritis was used to investigate the effect of pre-treatment with capsaicin on the symptoms of osteoarthritis induced by the injection of monosodium iodoacetate. This model mimics both histopathology and symptoms associated of human osteoarthritis. Injection of monosodium iodoacetate, an inhibitor of glycolysis, into the femorotibial joints of rodents promotes loss of articular trabecular bone and invokes pain symptoms similar to those noted in human osteoarthritis. Twenty rats were divided in two groups either receiving placebo or monosodium iodoacetate. Each group was subdivided in two groups either receiving pre-treatment with capsaicin two weeks before monosodium iodoacetate injection or not, resulting in four groups of five rats each. The impact of a single intra-articular administration of capsaicin (0.5%) on the generation of evoked mechanical pain (hind limb weight bearing, automated von Frey monofilament and RotaRod tests) and bone lesions (micro-CT scan radiographic analyses of bone structure) following monosodium iodoacetate-induced osteoarthritis in rats was determined. Evoked mechanical pain as monitored over a period of 4 weeks after monosodium iodoacetate injection was abolished in capsaicin pre-treated animals and pain values are comparable to those of capsaicin controls. Chronic joint pathological changes such as bone erosion and trabecular damage were significantly reduced by pre-treatment with a single administration of capsaicin. Decrease of bone volume was considerably ameliorated and trabecular connectivity was substantially better in capsaicin pre-treated animals. Capsaicin, an agonist activator of the vanilloid nociceptors (TRPV1), appears to be effective in protecting bone from arthritic damage. The present results support the hypothesis that capsaicin-sensitive sensory neurons contribute to bone lesions in the monosodium iodoacetate-induced osteoarthritis rat model.

Selected Abstracts From Other Journals

Background: Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study.

The Associations Between the Dominant and Nondominant Peak External Knee Adductor Moments During Gait in Healthy Subjects: Evidence for Symmetry

Teichtahl AJ, Wluka AE, Morris ME, Davis SR, Cicuttini FM. The associations between the dominant and nondominant peak external knee adductor moments during gait in healthy subjects: evidence for symmetry. Objectives There is growing interest in the role of the knee adduction moment in the pathogenesis of knee pain and osteoarthritis. It is unclear whether the knee adduction moment is similar between the dominant and nondominant legs during locomotion. This study examined whether asymmetry exists in the peak knee adductor moments during gait in healthy adults. Design Cross-sectional study. Setting Musculoskeletal Research Centre, La Trobe University, Melbourne, Victoria, Australia. Participants Three-dimensional Vicon gait analyses were performed for 17 healthy men and women. Interventions Not applicable. Main Outcome Measures The external dominant and nondominant peak knee adduction moments during early and late stance were analyzed to determine whether any significant differences occurred between limbs. Results Peak knee adductor moments for dominant and nondominant limbs were significantly correlated during early ( R=0.61, P=0.009) and late ( R=0.72, P=0.001) stance. After adjustment for age and sex, there was an associated 0.58 ( P=0.030) and 0.98 ( P=0.009) unit increase in the peak knee adduction moment in the nondominant leg, for every 1 unit increase in the dominant leg during the early and late stance phases of gait, respectively. Further evidence for symmetry was provided by the symmetry index, which was 0.04% and 0.62% for early and late stance, respectively. Conclusions In healthy subjects, the magnitude of the dominant limb peak external knee adduction moments during stance, and in particular late stance, appears representative of the magnitude of the moment in the nondominant limb. These findings imply symmetry between these moments and may have important implications when collecting data for limb analyses among healthy subjects. Whether gait symmetry protects against the onset of unilateral (or increases the risk for bilateral) pathological joint changes will need to be confirmed longitudinally.

Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial

Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study. We undertook a double-blind, randomised, placebo-controlled, crossover study at 24 sites in North America and Europe. Patients with active psoriatic arthritis were randomly allocated via interactive voice response system to either ustekinumab (90 mg or 63 mg) every week for 4 weeks (weeks 0-3) followed by placebo at weeks 12 and 16 (n=76; Group 1) or placebo (weeks 0-3) and ustekinumab (63 mg) at weeks 12 and 16 (n=70; Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to week 16, and patients were followed up to week 36 [corrected]. The primary endpoint was ACR20 response at week 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267956. At week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14.0-41.6]; p=0.0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33.2-60.6]; p<0.0001). During the placebo-controlled period (weeks 0-12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1). Ustekinumab significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions compared with placebo, and the drug was well tolerated. Larger and longer term studies are needed to further characterise ustekinumab efficacy and safety for treatment of psoriatic arthritis.

Role of ultrasound in assessment of early rheumatoid arthritis

This report reviews imaging methods used for diagnosis and monitoring of rheumatoid arthritis, with emphasis on the role of ultrasonography. Traditionally, conventional radiography has been useful in detecting and monitoring the extent of joint destruction in rheumatic disease. However, it is particularly difficult to detect pathological joint changes in the early stages. Magnetic resonance imaging is able to detect inflammation of the synovial membrane and erosions but is limited by cost and availability. Ultrasound has recently emerged as a useful and potentially reliable method for assessing the degree of joint inflammation and erosion in patients with early rheumatoid arthritis.

Quantitative Analysis of Micro-CT Imaging and Histopathological Signatures of Experimental Arthritis in Rats

Micro-computed tomographic (micro-CT) imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA), quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws (n = 10) stored in formalin consisted of approximately 600 30-mum slices acquired on a 512 x 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%). The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents.

Quantitative Analysis of Micro-CT Imaging and Histopathological Signatures of Experimental Arthritis in Rats

Micro-computed tomographic (micro-CT) imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA), quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws (n = 10) stored in formalin consisted of approximately 600 30-mum slices acquired on a 512 x 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%). The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents.

DEFORMITIES OF THE HAND INCIDENTAL TO PATHOLOGICAL CHANGES OF THE EXTENSOR AND INTRINSIC MUSCLE MECHANISMS

1. Metacarpophalangeal joints in extreme hyperextension of long duration in conjunction with absent intrinsic muscles may he treated expediently by joint fusion. 2. Metacarpophalangeal joints with less severe hyperextension and with functioning intrinsic muscle mechanism can be improved by the adequate excision of collateral ligaments, freeing of all dorsal tissues, and stripping of the volar plate. The heavy deep dorsal fascia in particular must be excised. 3. When the intrinsic strength of the index finger is being restored in the absence of contractures, it is advisable to replace weak lumbrical and volar interosseus muscles, as well as a weak first. dorsal interosseus. This strengthens volar abduction and gives a strong pinch. 4. If the dorsal hood is destroyed and the joint is affected, fibrous ankylosis or osseous fusion gives a desirable end result. 5. If the dorsal hood is intact and the extensor tendons are destroyed, it is desirable to correct the extension contracture by adequate excision of scar tissue and collateral ligaments, followed by the replacement of the extensor tendons. 6. In burns, a fixed button-hole deformity can be changed to a mallet deformity for better flexion,—that. is, for a golfer, if other reconstructive measures cannot be done. In old burns, it is important occasionally to maintain a slight button-hole deformity if this position is consistent with a specific occupation,—that is, for a piano player. 7. Fusion of the middle or distal interphalangeal joints is a useful procedure for irreparable flexion or extension deformities. 8. The intrinsic-plus hand, due to contracture of the intrinsic muscle mechanism, can be improved by advancing the intrinsic muscles in the metacarpal region or by sectioning the lateral bands opposite the proximal interphalangeal joints. 9. It is necessary to differentiate a contracture of the intrinsic muscles and fascia, contracture of the lateral bands in the digit only, contracture of both the extensor mechanism and lateral hands, and changes in the digits due to pathological joint changes resulting in hyperextension.