ABSTRACT
Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody-producing B cells. Activation of B cells is maintained within ectopic germinal centres found in affected joints. Fibroblast-like synoviocytes (FLS) present in inflamed joints support B-cell survival, activation, and differentiation. CD27+ memory B cells and naive B cells show very different responses to activation, particularly by CD40 ligand (CD40L). We show that FLS-dependent activation of human B cells is dependent on interleukin-6 (IL-6) and CD40L. FLS have been shown to activate both naive and memory B cells. Whether the activating potential of FLS is different for naive and memory B cells has not been investigated. Our results suggest that FLS-induced activation of B cells is dependent on IL-6 and CD40L. While FLS are able to induce plasma cell differentiation, isotype switching, and antibody production in memory B cells, the ability of FLS to activate naive B cells is significantly lower.
ABSTRACT
BACKGROUND This retrospective study used the Harris hip score (HHS) and range of motion (ROM) to compare gait before and after total hip arthroplasty using the modular S-ROM® hip prosthesis in 23 patients treated at a single center. MATERIAL AND METHODS For this study, 23 patients with severe hip deformity, who were treated with a total hip replacement using the S-ROM® modular hip system by DePuy® in the period from 2003 until 2008, underwent a 3-dimensional gait analysis before and after surgery. Values were compared with a validated data set of healthy subjects. Gait analysis took place using 8 infrared cameras (50 Hz), 2 force platforms of Advanced Medical Technology, Inc. (AMTI)®, and the Vicon® 512 system. The HHS and ROM of the hip joint were determined preoperatively and postoperatively. The follow-up period was 16.7±15.2 months. RESULTS A healthy gait pattern is characterized by an even stride length of both legs in relation to body height and relative symmetry of certain gait phases. These characteristics are influenced by the range of motion of the hip joint and by pelvic tilt. Symmetry could be achieved postoperatively in the stance phase and in the single-leg stance phase. However, the gait phases could not normalize. HHS and ROM improved postoperatively. CONCLUSIONS The findings from this retrospective study showed that ROM and HHS significantly improved following THA with the S-ROM® hip prosthesis, but that gait did not completely return to normal.
Subject(s)
Arthroplasty, Replacement, Hip , Gait Analysis , Hip Prosthesis , Aged , Biomechanical Phenomena , Female , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: "Advanced Core Decompression" (ACD) is a new technique for treatment of osteonecrosis of the femoral head (ONFH) that includes removal of the necrotic tissue using a percutaneous expandable reamer followed by refilling of the drill hole and the defect with an injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone graft substitute. As autologous bone has been shown to be superior to all other types of bone grafts, the aim of the study is to present and evaluate a modified technique of ACD with impaction of autologous bone derived from the femoral neck into the necrotic defect. METHODS: A cohort of patients with an average follow-up of 30.06 months (minimum 12 months) was evaluated for potential collapse of the femoral head and any reasons that led to replacement of the operated hip. Only patients in stages 2a to 2c according to the Steinberg classification were included in the study. RESULTS: In 75.9% the treatment was successful with no collapse of the femoral head or conversion to a total hip replacement. Analysis of the results of the different subgroups showed that the success rate was 100% for stage 2a lesions and 84.6% respectively 61.5% for stages 2b and 2c lesions. CONCLUSIONS: Previous studies with a comparable follow-up reported less favourable results for ACD without autologous bone. Especially in stages 2b and 2c the additional use of autologous bone has a positive effect. In comparison to other hip-preserving techniques, the modified ACD technique is a very promising and minimally invasive method for treatment of ONFH. TRIAL REGISTRATION: German clinical trials register ( DRKS00011269 , retrospectively registered).
Subject(s)
Bone Substitutes/adverse effects , Bone Transplantation/methods , Decompression, Surgical/methods , Femur Head Necrosis/surgery , Femur Neck/transplantation , Adult , Arthroplasty, Replacement, Hip/adverse effects , Bone Wires , Calcium Phosphates/adverse effects , Calcium Sulfate/adverse effects , Decompression, Surgical/instrumentation , Female , Femur Head Necrosis/pathology , Fluoroscopy/instrumentation , Fluoroscopy/methods , Follow-Up Studies , Humans , Male , Middle Aged , Organ Sparing Treatments/methods , Prospective Studies , Prosthesis Failure , Transplantation, Autologous/methods , Treatment Outcome , Young AdultABSTRACT
BACKGROUND Revitalizing the necrotic subchondral bone and preserving the intact cartilage layer by retrograde drilling is the preferred option for treatment of undetached osteochondral lesions of the talus (OLT). We assessed the effectiveness of Endoscopic Core Decompression (ECD) in treatment of OLT. MATERIAL AND METHODS Seven patients with an undetached OLT of the medial talar dome underwent surgical treatment using an arthroscopically-guided transtalar drill meatus for core decompression of the lesion. Under endoscopic visualization the OLT was completely debrided while preserving the cartilage layer covering the defect. The drill tunnel and debrided OLT were filled using an injectable bone graft substitute. Various clinical scores, radiographic imaging, and MRI were evaluated after a mean follow-up of 24.1 months. RESULTS The American Orthopedic Foot and Ankle Society Score significantly improved from 71.0±2.4 to 90.3±5.9, and the Foot and Ankle Disability Index improved from 71.8±11.1 to 91.7±4.8. Radiographically, we observed good bone remodelling of the medial talar dome contour within 3 months. In MRI, an alteration of the bony signal of the drill tunnel and the excised OLT remained for more than 12 months. CONCLUSIONS First follow-up results for the surgical technique described in this study are highly promising for treatment of undetached stable OLT grade II or transitional stage II-III according to the Pritsch classification. Even lesions larger than 150 mm2 showed good clinical scores, with full restoration of the medial talar dome contour in radiographic imaging.
Subject(s)
Decompression, Surgical/methods , Osteonecrosis/surgery , Talus/surgery , Adolescent , Adult , Aged , Ankle Joint/pathology , Ankle Joint/surgery , Arthroplasty/methods , Arthroscopy/methods , Cartilage, Articular/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Osteonecrosis/diagnostic imaging , Osteonecrosis/pathology , Pilot Projects , Talus/diagnostic imaging , Talus/pathology , Treatment OutcomeABSTRACT
PURPOSE: Treatment of full-thickness cartilage defects in the hip is a major issue for orthopaedic surgeons. Autologous matrix-induced three-dimensional chondrocyte transplantation using three-dimensional spheroids (ACT 3D) may be an option for treatment. The aim of the study is to describe the feasibility and first clinical results of ACT 3D with spheroids at the hip. METHODS: In this report, the surgical technique was described for the first time, and the outcome of sixteen patients with chondral defects induced by cam-type femoroacetabular impingement (FAI) who were followed up in a prospective study was evaluated. All patients underwent physical examination before the first surgery and again before the second (about 6 weeks later). Further examinations were performed 6 weeks after the second surgery and at an average follow-up period of 16.09 months. At every visit, the non-arthritic hip score (NAHS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) were obtained. In addition, patient satisfaction was evaluated during the last follow-up examination by means of a questionnaire. RESULTS: The NAHS and WOMAC scores had significantly improved 6 weeks after arthroscopic treatment of the cam-type FAI, and a further significant enhancement was seen 6 weeks after the second surgery with application of the chondrocyte spheroids. In the last follow-up, the mean results were equally as good as the second follow-up examination 12 weeks after surgery. CONCLUSIONS: The present study shows that ACT 3D using spheroids is a feasible method that can be easily performed during arthroscopy. As the first results have been encouraging, the ACT 3D with spheroids at the hip should be continued. More studies should be initiated to get an impression of the quality grade of this method in comparison with other treatment options in case of chondral defects at the hip. LEVEL OF EVIDENCE: III.
Subject(s)
Arthroscopy , Cartilage, Articular/surgery , Chondrocytes/transplantation , Hip Joint/surgery , Spheroids, Cellular/physiology , Adult , Cartilage, Articular/injuries , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Outcome Assessment , Patient Satisfaction , Prospective Studies , Tissue Engineering , Transplantation, Autologous , Young AdultABSTRACT
PURPOSE: Hip arthroscopy is a safe and reproducible method for treating femoroacetabular impingement (FAI) and has evolved greatly in recent years. But little is known about the influences on the outcome after surgery. The aims of the current study were to elucidate (1) which parameters can be used as a marker for the presence of chondral and labral lesions, (2) the postoperative clinical outcome, and (3) at which time after surgery recovery occurs. METHODS: A prospective study was performed with 177 patients who underwent hip arthroscopy because of cam-type FAI. The patients were examined preoperatively as well as 6 weeks and 6 months postoperatively, and their condition was rated according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Non-Arthritic Hip Score (NAHS). Statistical analyses were performed to evaluate the influence of independent factors such as "patient age," "pain duration before surgery" on the clinical outcome, and the appearance of chondral or labral defects. RESULTS: The NAHS and WOMAC scores showed a significant enhancement 6 weeks after surgery. Only the NAHS showed a further improvement after 6 months. A positive correlation with the dependent variable "chondral lesion" was evaluated for the independent variables "pain duration before surgery," "preoperative NAHS," and "labrum lesion". Using ROC analysis, the optimal cutoff value of "pain duration before surgery" as a predictor was 9.5 months, for the NAHS 42.5 points. For the dependent variable, "6-month postoperative NAHS" significant correlations for the independent variables "age" and "pain duration before surgery" were revealed with a cutoff value of 55.5 years, respectively, 23.5 months. CONCLUSIONS: It was concluded from the results that the date of surgery is relevant for the appearance of chondral defects. Patient age is a further relevant factor for clinical outcome. Recovery after hip arthroscopy takes place mainly in the first 6 weeks after surgery. LEVEL OF EVIDENCE: Therapeutic study, Level III.
Subject(s)
Arthroscopy/methods , Cartilage, Articular/injuries , Early Medical Intervention , Femoracetabular Impingement/surgery , Hip Joint/surgery , Adult , Female , Humans , Male , Middle Aged , Ontario , Postoperative Period , Prospective Studies , Radiography , Recovery of Function , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: To evaluate the feasibility of 3 Tesla (T) high-resolution and gadolinium enhanced MRI of cartilage (dGEMRIC) in the thin and rounded hip cartilage of patients after acetabular matrix-based autologous chondrocyte transplantation (MACT). METHODS: Under general ethics approval, 24 patients were prospectively examined 6-31 months after acetabular MACT at 3T using high-resolution proton-density weighted (PDw) images (bilateral PD SPACE, 0.8 mm isotropic; unilateral PD-TSE coronal/sagittal, 0.8 × 0.8 resp. 0.5 × 0.5 × 2.5 mm) as well as T1 mapping (3D-FLASH, 0.78 mm isotropic) in dGEMRIC technique, and clinically scored. The cartilage transplant was evaluated using an adapted MOCART score (maximum 85 points). T1 relaxation times were measured independently by two radiologists. Here, regions of interest were placed manually in automatically calculated relaxation-maps, both in the transplant and adjacent healthy cartilage regions. Interobserver reliability was estimated by means of intraclass-correlation (ICC). RESULTS: The transplant was morphologically definable in the PDw images of 23 patients with a mean MOCART score of 69 points (60-80 points, SD 6.5). T1 maps showed a clear differentiation between acetabular and femoral cartilage, but correlation with PDw images was necessary to identify the transplant. Mean T1 relaxation times of the transplant were 616.3 ms (observer 1) resp. 610.1 ms (observer 2), and of adjacent healthy acetabular cartilage 574.5 ms (observer 1) resp. 604.9 ms (observer 2). Interobserver reliability of the relaxation times in the transplant was excellent (ICC-coefficient 0.88) and in adjacent healthy regions good (0.77). CONCLUSION: High-resolution PDw imaging with adapted MOCART scoring and dGEMRIC is feasible after MACT in the thin and rounded hip cartilage.
Subject(s)
Cartilage, Articular/pathology , Chondrocytes/transplantation , Contrast Media/chemistry , Gadolinium/chemistry , Hip/pathology , Magnetic Resonance Imaging , Adult , Arthroscopy , Cell Transplantation , Chondrocytes/cytology , Feasibility Studies , Female , Gadolinium DTPA/chemistry , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Reproducibility of Results , Young AdultABSTRACT
OBJECTIVE: To analyze remodeling processes after advanced core decompression (ACD) in patients with avascular femoral head necrosis by means of 3T MRI and to identify indicators for clinical outcome considering the defect size and characteristics of the bone graft and of the neighboring regeneration tissue. MATERIALS AND METHODS: Thirty-four hips, with preexisting preoperative MRIs in 21 cases, were examined 1-34 months (mean 12.7) postoperatively by 3T MRI. The volume of necrosis was measured manually pre- and postoperatively to calculate absolute as well as percentage necrosis reduction. The signal intensity of the bone graft was quantified using a 4-point scale. Border phenomena between the bone graft and bone were described and classified into groups. Wilcoxon sign-rank test was used to identify correlations between the analyzed items and clinical signs of femoral head collapse after a mean follow-up time of 28.6 months (10.4-46.8). RESULTS: Mean percentage reduction of necrosis was significantly higher in asymptomatic patients (59.36%) compared to patients with signs of femoral head collapse (28.78%, p = 0.008). Signal intensity of the bone graft increased in T1w and T2w TIRM sequences over time after surgery and was significantly higher in asymptomatic patients. Five border phenomena between the bone graft and healthy bone were identified. Among them, the so-called "rail sign" representing three layers of remodeling tissue correlated with the histological observations. CONCLUSION: A variety of border phenomena representing remodeling processes have been described using 3T MRI. Beneath the percentage amount of necrosis reduction, we identified the signal intensity of the bone graft as an indicator for clinical outcome.
Subject(s)
Bone Transplantation , Decompression, Surgical , Femur Head Necrosis/surgery , Femur Head/surgery , Magnetic Resonance Imaging , Postoperative Complications/diagnosis , Bone Remodeling , Female , Femur Head/pathology , Femur Head Necrosis/pathology , Follow-Up Studies , Humans , Male , Middle Aged , Observer Variation , Postoperative Period , Treatment OutcomeABSTRACT
"Advanced core decompression" (ACD) is a treatment option for osteonecrosis of the femoral head (ONFH) that aims at complete removal of the necrotic tissue using a percutaneous expandable reamer and refilling of the head with an osteoconductive bone-graft substitute. The objective of this study was to evaluate if the success of ACD depends on the amount of necrotic tissue remaining after the procedure and how efficiently the necrotic tissue can be removed with the current reamer. Three-dimensional models of proximal femora including ONFH were generated from the preoperative MRIs of 50 patients who underwent ACD. Best-case removal was calculated by geometrical analysis. In 28 of 50 cases, postoperative MRI was used to determine how much necrotic tissue had been removed. Prognostic values and correlations were evaluated in order to assess success or failure of the treatment. The amount of preoperative and remaining necrosis correlates significantly with treatment failure. The larger both volumes are, the more likely it is that treatment will fail. In patients with remaining necrosis of less than 1000 mm(3), no treatment failure was observed. The amount of necrosis actually removed differed significantly from the amount calculated as the best possible result. Simulation of the removal procedure showed that complete removal is not possible. These results led to the conclusion that the success of ACD depends on the amount of necrotic tissue remaining in the femoral head after the procedure. Modifications to the instrument are necessary to increase the amount of necrotic tissue that can be removed.
Subject(s)
Decompression, Surgical/instrumentation , Femur Head Necrosis/surgery , Femur Head/surgery , Surgical Instruments , Equipment Design , Female , Femur Head Necrosis/diagnosis , Humans , Magnetic Resonance Imaging , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. MATERIAL/METHODS: Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of the iliac crest followed by density gradient centrifugation and flow cytometry with defined antigens (CD105+/73+/45-/14-). The cells were seeded and incubated as follows: without additives (Group 0; donor A/B/C), with 10(-7) M iloprost only (Group 0+ilo; A/B), with indomethacin only in concentrations of 10(-6) M (Group 1, A), 10(-5) M (Group 2, B), 10(-4) M (Group 3, A/B), and together with 10(-7) M iloprost (Groups 4-6, A/B/C). On Day 10 and 28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and donor) were performed to investigate cell proliferation (cell count measurement) and differentiation towards the osteoblastic lineage (CD34-, CD45-, CD105+, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist, specific ALP-activity). RESULTS: Indomethacin alone suppressed BMSC differentiation towards the osteoblastic lineage by downregulation of Runx2, Col1, and ALP. In combination with indomethacin, iloprost increased cell proliferation and differentiation and it completely suppressed Twist expression at Day 10 and 28. Iloprost alone did not promote cell proliferation, but moderately enhanced Runx2 and Twist expression. However, the proliferative effects and the specific ALP-activity varied donor-dependently. CONCLUSIONS: Iloprost partially antagonized the suppressing effects of indomethacin on BMSC differentiation towards the osteoblast lineage. It enhanced the expression of Runx2 and, only in the presence of indomethacin, it completely suppressed Twist. Thus, in the treatment of avascular osteonecrosis or painful bone marrow edema, the undesirable effects of indomethacin might be counterbalanced by iloprost.
Subject(s)
Bone Marrow Cells/cytology , Epoprostenol/pharmacology , Indomethacin/pharmacology , Mesenchymal Stem Cells/metabolism , Nuclear Proteins/metabolism , Twist-Related Protein 1/metabolism , Adult , Alkaline Phosphatase/metabolism , Antigens, CD/metabolism , Cell Count , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Collagen Type I/metabolism , Core Binding Factor Alpha 1 Subunit/metabolism , Epoprostenol/administration & dosage , Female , Humans , Iloprost/pharmacology , Immunohistochemistry , Indomethacin/administration & dosage , L-Lactate Dehydrogenase/metabolism , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Osteocalcin/metabolismABSTRACT
Total hip arthroplasty (THA) is one of the most successful operations that can restore function and relieve pain. Although a majority of the patients achieve significant pain relief after THA, there are a number of patients that develop chronic pain for unknown reasons. A literature search was performed looking for chronic pain after total hip arthroplasty and stable THA. Major causes of chronic pain include aseptic loosening or infection. However, there is a subset of patients with a stable THA that present with chronic pain which can have several aetiologies. These include soft tissue, bony, neurological, vascular and psychological causes. Essential for successful treatment is the ability to make the correct diagnosis. Thus therapy may be either non-operative or operative. In addition, diagnosis and management often may require multidisciplinary approaches to successfully alleviate chronic pain in these patients with a stable prosthesis.
Subject(s)
Arthroplasty, Replacement, Hip , Pain, Postoperative/etiology , Pain, Postoperative/therapy , Humans , Pain Management , Pain Measurement , Risk FactorsABSTRACT
PURPOSE: Correct alignment of the rotation of the femoral component and the flexion gap after total knee arthroplasty is difficult in patients with preoperative leg axis deviation. Inaccuracy may result in problems with the patellofemoral joint and instability, in particular. We examined the influence of the preoperative leg axis on the rotation of the femoral component and the symmetry of the flexion gap after total knee arthroplasty using the tibial-cut-first technique. METHODS: A retrospective study was carried out of 58 consecutive patients who underwent primary LCS total knee arthroplasty using the tibial-cut-first technique in 2008 based on preoperative full-leg radiographs and the final radiographs taken according to Kanekasu's technique. The patients were divided into three groups (varus-valgus-neutral) according to their preoperative leg axis. RESULTS: Using the tibial-cut-first technique, a mean neutral rotation of the femoral component of 0.5° and a mean symmetrical flexion gap of -0.7° were achieved. Nevertheless, there was a positive correlation of the preoperative leg axis with the rotation of the femoral component. The differences in the rotation of the femoral component and the flexion gap between the three groups were not significant. The only significant difference between the varus and valgus groups was the extent of rotation of the femoral component, with a slightly greater external rotation of 2.7° in the valgus group. CONCLUSIONS: This study suggests that it is possible to achieve correct rotational alignment of the femoral component and a symmetrical flexion gap using the tibial-cut-first technique in patients with a preoperatively deviated leg axis.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Femur/anatomy & histology , Knee Joint/anatomy & histology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , RotationABSTRACT
INTRODUCTION: Plain radiography, bone scintigraphy, digital subtraction arthrography and various other techniques can be used to evaluate loosening of hip replacements. These methods are associated with radiation exposure and some of them have an increased morbidity. Furthermore, in some cases the results are not conclusive. METHOD: The osteoclast biomarkers tartrate-resistant acid phosphatase 5b (TRAP 5b) and C-terminal telopeptides of type I collagen (CTX) in serum taken from 12 patients with aseptic loosening were measured. Serum samples from 24 other patients, 12 with an intact arthroplasty and 12 without any kind of joint replacement, served as control groups. RESULTS: The serum level of CTX was increased in comparison to the control groups, but the differences were not significant. In contrast, the increase in TRAP 5b in patients with aseptic loosening was highly significant (P < 0.001). A TRAP 5b value of 3.365 U/L was determined as a cut-off value, giving a sensitivity of 83.3% and specificity of 91.7% to differentiate the patients with aseptic loosening from those with an intact arthroplasty. Measurement of serum TRAP 5b may be a clinically relevant assay for monitoring patients after arthroplasty.
Subject(s)
Acid Phosphatase/blood , Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Isoenzymes/blood , Peptide Fragments/blood , Procollagen/blood , Prosthesis Failure , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Collagen Type I , Female , Humans , Male , Middle Aged , Peptides , Tartrate-Resistant Acid PhosphataseABSTRACT
One of the main problems after total knee arthroplasty is pain in the patellofemoral joint, which in some cases leads to revision surgery. Rotation of the femoral component has a significant influence on the path followed by the patella within the patellofemoral joint. We examined the influence of rotation of the femoral component after total knee arthroplasty on patellar tilt. We retrospectively analysed the radiographs of 48 patients who underwent primary LCS total knee arthroplasty without patella resurfacing and without lateral release. Rotation of the femoral component was determined using Kanekasu's technique and patellar tilt assessment according to Laurin on Merchant's views. This radiographic study confirmed a highly significant correlation between external rotation of the femoral component and a decrease in patellar tilt following TKA. Furthermore, we found a highly significant correlation between pre- and postoperative patellar tilt angle.
Subject(s)
Arthroplasty, Replacement, Knee , Femur/diagnostic imaging , Patellofemoral Joint/diagnostic imaging , Humans , RadiographyABSTRACT
Cannabidiol (CBD) is a non-intoxicating phytocannabinoid from cannabis sativa that has demonstrated anti-inflammatory effects in several inflammatory conditions including arthritis. However, CBD binds to several receptors and enzymes and, therefore, its mode of action remains elusive. In this study, we show that CBD increases intracellular calcium levels, reduces cell viability and IL-6/IL-8/MMP-3 production of rheumatoid arthritis synovial fibroblasts (RASF). These effects were pronounced under inflammatory conditions by activating transient receptor potential ankyrin (TRPA1), and by opening of the mitochondrial permeability transition pore. Changes in intracellular calcium and cell viability were determined by using the fluorescent dyes Cal-520/PoPo3 together with cell titer blue and the luminescent dye RealTime-glo. Cell-based impedance measurements were conducted with the XCELLigence system and TRPA1 protein was detected by flow cytometry. Cytokine production was evaluated by ELISA. CBD reduced cell viability, proliferation, and IL-6/IL-8 production of RASF. Moreover, CBD increased intracellular calcium and uptake of the cationic viability dye PoPo3 in RASF, which was enhanced by pre-treatment with TNF. Concomitant incubation of CBD with the TRPA1 antagonist A967079 but not the TRPV1 antagonist capsazepine reduced the effects of CBD on calcium and PoPo3 uptake. In addition, an inhibitor of the mitochondrial permeability transition pore, cyclosporin A, also blocked the effects of CBD on cell viability and IL-8 production. PoPo3 uptake was inhibited by the voltage-dependent anion-selective channel inhibitor DIDS and Decynium-22, an inhibitor for all organic cation transporter isoforms. CBD increases intracellular calcium levels, reduces cell viability, and IL-6/IL-8/MMP-3 production of RASF by activating TRPA1 and mitochondrial targets. This effect was enhanced by pre-treatment with TNF suggesting that CBD preferentially targets activated, pro-inflammatory RASF. Thus, CBD possesses anti-arthritic activity and might ameliorate arthritis via targeting synovial fibroblasts under inflammatory conditions.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Cannabidiol/metabolism , Cannabidiol/pharmacology , Aged , Arthritis, Rheumatoid/metabolism , Calcium/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Male , Matrix Metalloproteinase 3/metabolism , Middle Aged , Synovial Fluid/drug effects , Synovial Membrane/metabolism , TRPA1 Cation Channel/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Synovial fibroblasts (SF) were reported to produce B cell activating factor (BAFF) in response to stimulation with interferon-γ (IFN-γ) or tumor necrosis factor (TNF). However, the influence of these pro-inflammatory cytokines on other receptors/ligands of the TNF superfamily or associated cytokine receptors in SF has not been investigated yet. Here we show the differential regulation of BAFF (CD257), Fn14 (CD266), TACI (CD267), BAFF-R (CD268), BCMA (CD269), CD40 ligand (CD40L, CD154), IFN-γR (CD119), Leptin receptor (ObR, CD295), VCAM-1 (CD106) and membrane TGF-ß in isolated SF and the impact of IFN-γ/TNF co-incubation on proliferation, IL-6 and IL-8 production. In addition, the impact of differentially stimulated SF on B cell survival in co-cultures was assessed. Surface cytokines and cytokine receptors were detected by flow cytometry. Soluble cytokine receptors and cytokines were quantified by ELISA. Proliferation was assessed by cell titer blue. Murine B cell survival in fibroblast/ B cell co-cultures was determined by annexin V/propidium iodide staining and flow cytometry. IFN-γ together with TNF synergistically and significantly increased the cell surface levels of BAFF, Fn14, TACI, BAFF-R, BCMA, CD40L, ObR and IFN-γR in rheumatoid arthritis SF after 72 h incubation. Soluble BAFF was only induced by IFN-γ and inhibited by TNF. Addition of TWEAK had no influence on proliferation or IL-8 production but decreased TNF-induced IL-6 production, whereas APRIL, BAFF and leptin did not modulate TNF or TNF/IFN-γ-induced proliferation or cytokine production. Proliferation was increased by TNF and further enhanced by the addition of IFN-γ. In co-culture experiments, SF stimulated with TNF/IFN but not TNF or IFN-γ alone increased shedding of VCAM-1 and expression of membrane TGFß, which was associated with reduced survival of murine B cells. IFN-γ and TNF regulate the expression of TNF family member cytokines and associated receptors. Ligation of IFN-γR and Fn14 under pro-inflammatory conditions modulated IL-6/IL-8 production and proliferation. In B cell/SF co-cultures, the combination of TNF/IFN reduced B cell survival possibly via enhanced VCAM-1 shedding and/or increased TGF-ß production. IFN-γ is necessary for the observed effects on B cell survival and SF cytokine production and emphasizes its anti-inflammatory role in rheumatoid arthritis.
Subject(s)
Arthritis, Rheumatoid/immunology , B-Cell Activating Factor/metabolism , B-Lymphocytes/cytology , Interferon-gamma/pharmacology , Synovial Membrane/cytology , Tumor Necrosis Factor-alpha/pharmacology , Aged , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , Cell Proliferation/drug effects , Cell Survival , Cells, Cultured , Coculture Techniques , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Male , Mice , Middle Aged , Receptors, Cytokine/drug effects , Receptors, Cytokine/metabolism , Synovial Membrane/drug effects , Synovial Membrane/metabolismABSTRACT
The so-called "Advanced Core Decompression" (ACD) is a new option that tries to remove the necrotic tissue in patients with osteonecrosis of the femoral head (AVN) in a minimally invasive way by the use of a percutaneous expandable reamer and refilling with a resorbable and osteoinductive bone-graft substitute. Seventy-two hips of sixty patients with a mean follow-up of 29.14 months after ACD have been included in this study. Patients underwent physical examination preoperatively and six weeks after surgery as well as at two further follow-ups. Certain phases in disease progression and size of the necrotic lesion were differentiated on the basis of the classification of osteonecrosis of the femoral head by Steinberg.The femoral heads had collapsed in 24 cases (33%). Analysis of the survival rates with regard to defect size revealed that the largest defects had a significantly higher rate of femoral head collapse than the smaller defects. Clinical scores were also depending on defect size but also on disease stage. The current ACD technique has not yet achieved any significant improvement in the success rate of core decompression procedures. It can be concluded that the success of ACD depends especially on the defect size. Copyright © 2015 John Wiley & Sons, Ltd.
Subject(s)
Decompression, Surgical/methods , Adult , Aged , Female , Follow-Up Studies , Hip Prosthesis , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Odds Ratio , Visual Analog Scale , Young AdultABSTRACT
The treatments of avascular osteonecrosis (AVN) include both conservative and surgical methods which are dependent on the stage and progression of the disease. The vasoactive-prostaglandin-analogue iloprost (PGI2) has been utilized in several areas of medicine and recently has been used for the treatment of AVN. A total of 108 patients with 136 osteonecrosis of different joints, etiology and severity were treated with iloprost. The mean follow-up was 49.71 months: range 15-96 months, and outcome measurements recorded regarding subjective complaints, visual analog scale (pain), function and survival. The outcome scores used include the Harris Hip Score, Knee Society score, Foot and Ankle Survey, visual analogue scale (VAS) and a separate questionnaire. The location and etiology of AVN in our study demonstrated the typical pattern. All of the observed side effects of the therapy were minor and completely reversible. Most of patients (74.8%) showed a significant improvement of subjective complaints and decrease in VAS pain scores after the treatment with iloprost. However, 20% of the treated joints with the stadium Association for Research on Osseous Circulation (ARCO) grade 2, 71% with ARCO 3 and 100% with ARCO 4 underwent subsequent total joint replacement. The medical treatment of bone marrow edema or avascular osteonecrosis by Iloprost provides an safe and effective alternative strategy in the management of AVN presenting in the early stages (ARCO 1 or 2). For more advanced stages (ARCO 3 or 4), surgical intervention should be prioritized.
ABSTRACT
Aseptic necrosis of the femoral head (AVN) leads to destruction of the affected hip joint, predominantly in younger patients. Advanced core decompression (ACD) is a new technique that may allow better removal of the necrotic tissue by using a new percutaneous expandable reamer. A further modification is the refilling of the drill hole and the defect with an injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone graft substitute. Compression tests were performed on seven pairs of femoral cadaver bones. One femur of each pair was treated with ACD, while the opposite side remained untreated. Clinically, the postoperative outcome of 27 hips in 23 patients was performed by physical examination 6 weeks after ACD and at average follow-up of 9.69 months, and compared with the preoperative results. MRI was used to assess the removal of the necrotic tissue, any possible progression of AVN and evaluation of collapse. In the biomechanical analysis, the applied maximum compression force that caused the fracture did not significantly differ from the untreated opposite side. The overall results of postoperative physical examinations were significantly better than preoperatively. Five hips (18.5%) were converted to a total hip replacement. The follow-up MRIs of the other patients showed no progression of the necrotic area. The first follow-up results of ACD have been encouraging for the early stages of aseptic necrosis of the femoral head. In our opinion, an assured advantage is the high stability of the femoral neck after ACD, which allows quick rehabilitation.
Subject(s)
Decompression, Surgical/methods , Femur Head Necrosis/surgery , Adult , Aged , Biomechanical Phenomena , Female , Femur Head Necrosis/diagnostic imaging , Femur Head Necrosis/pathology , Femur Head Necrosis/physiopathology , Fluoroscopy , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Postoperative Care , Preoperative Care , Treatment OutcomeABSTRACT
Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The purpose of the current study was to evaluate cellular senescence of macrophages and giant cells in patients with aseptic hip loosening by determination of SA-ß-Gal (SA-ß-galactosidase), a reliable and frequently used indicator of cellular senescence. The level of senescence in capsule and interface membranes was significantly higher in patients with aseptic loosening in comparison to specimens from patients without aseptic loosening. Using Spearman's rank correlation, we found that the expression of SA-ß-Gal in giant cells (p=0.002) and macrophages (p=0.050) in the interface membranes correlates significantly with the degree of polyethylene debris. We speculate that the induction of DNA damage by wear particles is responsible for premature senescence. Consequently, we conclude that the form of senescence observed in this study is a "stress-induced senescence".