Synovial Reaction Research Articles

Toll-Like Receptor 4 (TLR4) Stimulates Synovial Injury of Temporomandibular Joint in Rats Through the Activation of p38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.

BackgroundSynovitis is an important disease that cause intractable pain in temporomandibular joint (TMJ), and the inflammation process played a crucial role in the initiation and development of temporomandibular joint disorder. A series of investigations suggested that the increasing expression of interleukin-(IL) 1β secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In this present study, we investigated the signaling pathways which regulate the expression of IL-1β.Material/MethodsThe occlusal interference animal model was created to induce synovial injury. Forty-eight rats were divided into 4 groups: 1) control group, 2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor targeting the p38) group. The inflammation changes were observed, and the expression of p38 and IL-1β in the synovial membranes were assayed.ResultsThe results showed that downstream p38 MAPK (mitogen-activated protein kinase) signaling was triggered following the activation of TLR4. Moreover, the injection of SB203580 could inhibit the inflammatory reactions and the increased expression of IL-1β at both mRNA and protein levels.ConclusionsThe results prompted us that TLR4 may stimulates synovial inflammatory reactions and increased expression of IL-1β in rats through the activation of p38 MAPK signaling pathway, p38 was an important mediator in the mechanisms of the initiation and development of synovial injury by regulating the expression of IL-1β in synovial membranes.

Intra-Articular Biocompatibility of Multistranded, Long-Chain Polyethylene Suture Tape in a Canine ACL Model.

The purpose of this study was to assess intra-articular use of a nonabsorbable braided suture tape for its biocompatibility when implanted adjacent to the native anterior cruciate ligament (ACL) in a canine model. Establishing biocompatibility of suture tape in the knee is an important foundational step for clinicians considering use of suture tape augmentation for ACL reconstruction or repair. The study hypothesis was that a nonabsorbable braided suture tape would be biocompatible in the knee with no resultant adverse functional consequences, and no significant intra-articular synovial reactions or articular cartilage degeneration attributable to direct exposure to the suture tape, whether intact or transected. Nonabsorbable braided suture tape was arthroscopically implanted adjacent to the native ACL of dogs (n = 6). The suture was intact in half of the dogs and was transected in the other half as a "worst-case" scenario. Dogs were assessed for postoperative complications and morbidity. Arthroscopic grading of synovium and cartilage was performed at 4 and 6 months. Histologic assessments were performed at the 6-month endpoint and compared with the ACL partial tear (n = 9) and ACL reconstruction (n = 5) cohorts as well as historical sham controls. No postoperative complications were noted. No animal developed lameness or clinical dysfunction, and there were no severe inflammatory or immune responses, cartilage erosions, or premature osteoarthritis noted. Arthroscopic assessments revealed no to mild synovitis and no apparent cartilage damage in either group. Histologically, both the intact and transected suture tape groups were associated with significantly (p ≤ 0.05) less synovial and articular cartilage pathology compared with the partial ACL transection and patellar bone-tendon-bone ACL autograft reconstruction cohorts, and matched historical sham controls. The hypothesis was accepted as study results support the biocompatibility of suture tape in the canine knee.

Hypothermia Promotes Cell-Protective and Chondroprotective Effects After Blunt Cartilage Trauma

Background: Cryotherapy is routinely administered after sports injuries of synovial joints. Although positive clinical effects on periarticular swelling and pain have been described, the effects on the cell biological activities of cartilage and synovial cells remain largely unknown so far. Hypothesis: Local hypothermia alleviates synovial reactions and prevents chondrocyte death as well as cartilage destructive processes after blunt cartilage trauma. Study Design: Controlled laboratory study. Methods: Human cartilage explants were impacted by a drop-tower apparatus (0.59 J) and cultured at 24 hours or 7 days in different temperature conditions (2 hours [short term], 16 hours [medium term], or throughout [long term] at 27°C; afterwards or throughout at 37°C). Besides, isolated human fibroblast-like synoviocytes (FLS) were stimulated with traumatized cartilage conditioned medium and cultured as mentioned above up to 4 days. The effects of hypothermia were evaluated by cell viability, gene expression, type II collagen synthesis and cleavage, as well as the release of matrix metalloproteinase (MMP)–2, MMP-13, and interleukin 6 (IL-6). Results: Seven days after trauma, hypothermic treatment throughout improved cell viability (short term: 10.1% [P = .016]; medium term: 6% [P = .0362]; long term: 12.5% [P = .0039]). Short-term hypothermia attenuated the expression of catabolic MMP-13 (mRNA: –2.2-fold [P = .0119]; protein: –2-fold [P = .0238]). Whereas type II collagen synthesis (1.7-fold [P = .0227]) was increased after medium-term hypothermia, MMP-13 expression (mRNA: –30.8-fold [P = .0025]; protein: –10.3-fold [P < .0001]) and subsequent cleavage of type II collagen (–1.1-fold [P = .0489]) were inhibited. Long-term hypothermia further suppressed MMP release (pro–MMP-2: –3-fold [P = .0222]; active MMP-2: −5.2-fold [P = .0183]; MMP-13: −56-fold [P < .0001]) and type II collagen breakdown (–1.6-fold [P = .0036]). Four days after FLS stimulation, hypothermia significantly suppressed the gene expression of matrix-destructive enzymes after medium-term (MMP-3: –4.1-fold [P = .0211]) and long-term exposure (a disintegrin and metalloproteinase with thrombospondin motifs 4 [ADAMTS4]: –4.3-fold [P = .0045]; MMP-3: –25.8-fold [P = .014]; MMP-13: –122-fold [P = .0444]) and attenuated IL-6 expression by trend. Conclusion: After blunt cartilage trauma, initial hypothermia for only 2 hours and/or 16 hours induced significant cell-protective and chondroprotective effects and promoted the anabolic activity of chondrocytes, while the expression of matrix-destructive enzymes by stimulated FLS was attenuated by prolonged hypothermia. Clinical Relevance: The findings of this preliminary ex vivo investigation indicate that optimized cryotherapy management after cartilage trauma might prevent matrix-degenerative processes associated with the pathogenesis of posttraumatic osteoarthritis.

Cartilage Repair with Mesenchymal Stem Cells (MSCs) Delivered in a Novel Chondroitin Sulfate / Polyethylene Glycol Hydrogel in a Rabbit Animal Model”

Objectives:To determine whether rabbit bone marrow-derived MSCs embedded in a chondroitin sulfate (ChS)/ poly (ethylene glycol) (PEG) biodegradable hydrogel display enhanced in vivo chondrogenesis as compared to ChS/PEG hydrogel alone, in a critical sized osteochondral defect in a rabbit animal model.Methods:Allogenic MSCs were harvested from bone marrow and expanded in specific media (20% fetal bovine serum, 50 U ml-1 penicillin, 50 mg ml-1 streptomycin, 20 mg ml-1 gentamicin, and 5 ng ml-1 bFGF (fibroblast growth factor) in low glucose Dulbecco’s modified Eagle media) under standard cell culture conditions (37o C with 5% CO2). Surgery was carried out in 10 mature New Zealand white rabbits (8 months old). A critical sized chondral defect (3mm) was performed bilaterally in the trochlear groove of the femoropatellar joint in all ten rabbits. Three treatment groups were established as follows: 1- hydrogel alone (5N), 2- hydrogel with MSCs (3 x 106 cell/ml) (5N), and 3- control defect with no treatment (10N). Animals were left to ambulate freely after surgery. At 6 months postoperative, euthanasia was performed. Macroscopic evaluation of defect repair was performed by four observers unaware of treatment groups using ICRS (International Cartilage Repair Society) scoring. Microscopic evaluation was performed using the O’Driscoll grading system. Using SigmaPlot 11.0 statistical software (Systat Software, San Jose, CA, USA), comparison between groups was performed with an ANOVA test to see if differences existed between treatment groups. Tukey’s correction was used to adjust for multiple group comparisons, and two independent t-tests: 1- between rabbits receiving hydrogel alone vs. their respective controls; 2- between rabbits receiving hydrogel / MSCs vs. their respective controls; for both ICRS and O’Driscoll scores, being a total of six statistical analyses.Results:At time of euthanasia, all hydrogels remained in place. There was no synovial reaction or macroscopic inflammation. Cartilage repair was evident in all groups. Macroscopically, no significant difference was evident according to ICRS scores. The average ICRS score for the groups was: 1 (hydrogel alone): 10 ± 1.73 SD, 2 (hydrogel with MSCs): 10 ± 1.41 SD and 3(control): 11.3 ± 1.06 SD (p= 0.088). Histological average scoring with O’Driscoll system for each group was highest for the hydrogel alone (1: 19.8 ± 5.5 SD, 2: 16 ± 3.54 SD, and 3: 18.5 ± 3.63 SD) (p= 0.227) (Figure 1). One way ANOVA, showed no statistical difference for both ICRS and O’Driscoll scores. The t-tests showed no statistical significance among groups (p>.05), except for ICRS score comparing control vs. hydrogel / MSCs which favored the control group (p=0.046).Conclusion:Hydrogels remained in place and induced chondrogenesis, especially when hydrogels were placed in the defect without MSCs. Adding MSCs to the hydrogel did not improve cartilage healing. Macroscopically, ICRS score was significantly worse for the MSCs/hydrogel group when compared to the control group. Limitations of this study include small animal model with natural good intrinsic cartilage regeneration. Still, all selected animals were mature, reducing the chances of natural healing. In addition, all animals had an established control defect. Future experiments will include adding transforming growth factor (TFGb) to the encapsulated MSCs to potentially improve chondrogenesis.

MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.

Controlling Abnormal Joint Movement Inhibits Response of Osteophyte Formation.

Objective Osteoarthritis (OA) is induced by accumulated mechanical stress to joints; however, little has been reported regarding the cause among detailed mechanical stress on cartilage degeneration. This study investigated the influence of the control of abnormal joint movement induced by anterior cruciate ligament (ACL) injury in the articular cartilage. Design The animals were divided into 3 experimental groups: CAJM group ( n = 22: controlling abnormal joint movement), ACL-T group ( n = 22: ACL transection or knee anterior instability increased), and INTACT group ( n = 12: no surgery). After 2 and 4 weeks, the knees were harvested for digital microscopic observation, soft X-ray analysis, histological analysis, and synovial membrane molecular evaluation. Results The 4-week OARSI scores showed that cartilage degeneration was significantly inhibited in the CAJM group as compared with the ACL-T group ( P < 0.001). At 4 weeks, the osteophyte formation had also significantly increased in the ACL-T group ( P < 0.001). These results reflected the microscopic scoring and soft X-ray analysis findings at 4 weeks. Real-time synovial membrane polymerase chain reaction analysis for evaluation of the osteophyte formation-associated factors showed that the mRNA expression of BMP-2 and VEGF in the ACL-T group had significantly increased after 2 weeks. Conclusions Typically, abnormal mechanical stress induces osteophyte formation; however, our results demonstrated that CAJM group inhibited osteophyte formation. Therefore, controlling abnormal joint movement may be a beneficial precautionary measure for OA progression in the future.

ACL Revision in Synthetic ACL graft failure

The development of synthetic grafts as an alternative to biological grafts for reconstruction of the anterior cruciate ligament dates from 1980. The interest is awakened due to the potential advantages of: The absence of morbidity associated with donor site, and early return to sport. However, this surgical technique has had multiple complications associated with graft: mechanical failures (synthetic graft failure, loss of fixation), synovial foreign body reaction, recurrent stroke, recurrent instability and ultimately, early osteoarthritis.Objectives:We describe the synthetic graft failure LCA, intraoperative findings and details of surgical technique.Methods:Patient 35 years old, with a history of ACL reconstruction four years of evolution in another health center, consultation with the Service knee arthroscopy for acute knee pain left knee during secondary sporting event to a rotation mechanism with fixed foot. On physical examination, presents and positive Lachman maneuver Pivot. Radiografia in a widening of the tibial tunnel is observed. NMR shows a discontinuity of fibers of synthetic graft.Results:First time arthroscopic revision where synthetic plastic LCA identifies with Disruption fiber pattern. Intraoperatively, hypertrophic chronic synovitis localized predominantly in intercóndilo is observed. debridement thereof is performed, and proceeds to the extraction of the synthetic ligament. Then he was made prior cruentado and revival of the edges of the tunnel, filling them with non-irradiated structural bone allograft. At four months as planned and after confirmation by studies incorporating bone graft was performed the second time with the new plastic ACL. It was planned like a primary graft surgery with autologous hamstring prepared in fourfold form, and fixation with modified transtibial technique Biotransfix system proximal and distal screw Biocomposite (arthrex®). A quadruple graft 9 mm was obtained, making good positioning of tunnels and stable fixation.Conclusion:While ACL reconstruction with synthetic graft has favorable medium-term results, the proportion of patients with complications of irreversible nature and high rates of dissatisfaction in the long term we are inclined to dismiss the indication of this technique in primary ACL reconstruction, to despite the potential benefits it offers.

Incidence of Adverse Reactions to Metal Debris From 28-mm Metal-on-Metal Total Hip Arthroplasties With Minimum 10 Years of Follow-Up: Clinical, Laboratory, and Ultrasound Assessment of 44 Cases

BackgroundTotal hip arthroplasty with metal-on-metal (MoM) bearings has been suspected to cause adverse reactions to metal debris (ARMD), with the incidence varying greatly by implant type and patient gender. The prevalence of ARMD from small-diameter MoM bearings in women is unknown, especially after 10 years of follow-up (FU). MethodsCementless 28-mm MoM total hip arthroplasty bearings (Metasul) were implanted consecutively in 42 active women between 1996 and 2002. They were reviewed after a minimum of 10 years' FU with clinical, laboratory, radiological, and ultrasound assessments. ResultsMean FU was 15.9 years (range, 13-18). The mean Postel-Merle d'Aubigné and Oxford scores were 16.9 (range, 13-18) and 15.1 (range, 12-24), respectively, at FU. Mean cup inclination angle was 46.3° (range, 35°-57°). No femoral osteolysis was detected, but limited acetabular osteolysis (11%) over the screw holes occurred in 5 cases. No liquid or solid synovial reactions or ARMD were apparent on ultrasound, even in the 5 cases of pelvic osteolysis. Mean chromium levels were 1.32 μg/L (range, 0.1-7.9) and cobalt levels were 1.85 μg/L (range, 0.35-13.6). Cobalt was >3 μg/L in only 3 cases. The 15.9-year survivorship was 95% (range, 94.1%-98.9%). ConclusionReliable results were obtained with 28-mm MoM bearings, notably in young, active patients. This implant configuration requires very accurate positioning. No ARMD was seen in this group at 16 years' FU.

Early changes in the knee of healer and non-healer mice following non-invasive mechanical injury.

In this study, we examined early time-dependent changes in articular cartilage and synovium in response to tibial compression and sought the plausible origin of cells that respond to compression in the healer (LGXSM-6) and non-healer (LGXSM-33) recombinant inbred mouse strains. The right knee of 13-week old male mice was subjected to tibial compression using 9N axial loading. The contralateral left knee served as a control. Knees were harvested at 5, 9, and 14 days post-injury. Histological changes in cartilage and synovium, immunofluorescence pattern of CD44, aggrecan, type-II collagen, cartilage oligomeric matrix protein and the aggrecan neo-epitope NITEGE, and cell apoptosis (by TUNEL) were examined. We used a double nucleoside analog cell-labeling strategy to trace cells responsive to injury. We showed that tibial compression resulted in rupture of anterior cruciate ligament, cartilage matrix loss and chondrocyte apoptosis at the injury site. LGXSM-33 showed higher synovitis and ectopic synovial chondrogenesis than LGXSM-6 with no differences for articular cartilage lesions. With loading, an altered pattern of CD44 and NITEGE was observed: cells in the impacted area underwent apoptosis, cells closely surrounding the injured area expressed CD44, and cells in the intact area expressed NITEGE. Cells responding to injury were found in the synovium, subchondral bone marrow and the Groove of Ranvier. Taken together, we found no strain differences in chondrocytes in the early response to injury. However, the synovial response was greater in LGXSM-33 indicating that, at early time points, there is a genetic difference in synovial cell reaction to injury. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:524-536, 2017.

Primary Non-Hodgkins Lymphoma Mimicking Lateral Epicondylitis

Primary bone lymphoma constitutes 3-7% of all malign bone tumors and extra-nodal lymphomas. Joint infiltration is very rare clinical entity and mono arthritis may be a secondary synovial reaction to adjacent bone disease or direct synovial involvement. Radiological features of primary lymphoma of bone may present with different findings. Lateral epicondylitis is one of the most causes of elbow pain. It is usually observed between 30 and 50 years of age. The main symptom is the pain at the lateral epicondyle of the elbow. We report a case of primary Non-Hodgkin's Lymphoma mimicking lateral epicondylitis a 61 years female patient. It emphasizes the need for a high clinical suspicion in susceptible cases, particularly in permanent bone and joint pain.

Increased 18F-FDG uptake suggests synovial inflammatory reaction with osteoarthritis: preliminary in-vivo results in humans.

The aim of this prospective study was to compare the metabolic activity of the knee joints of a group of patients with painful knees clinically (such as recurrent joint pain, joint instability, and functional limitations) consistent with osteoarthritis and those of another group of patients without such complaints, using [F]-2-fluoro-2-deoxy-D-glucose (F-FDG)-PET imaging. A total of 97 patients who participated in either painful joint prosthesis or diabetic foot research studies involving F-FDG-PET scans were asked to complete a knee pain questionnaire. The patients were asked whether they experienced pain in any joint, and if so, which joints were affected. A total of 18 knee joints without prosthesis were reported to be painful. The maximum standardized uptake values (SUVmax) of the middle joint space and lateral synovial tissue of these 18 knees were measured and compared with those of a set of patients with control asymptomatic knees. The average SUVmax of the middle part of the joint space in the painful knees was 1.35±0.59 compared with an average SUVmax value of 0.86±0.14 in the control group (P=0.0176). The average SUVmax of the synovium in the lateral part of the painful joints was 1.17±0.49 compared with 0.73±0.31 in the control group (P=0.0161). These data indicate that increased F-FDG uptake is associated with knee pain in osteoarthritis patients and that there is a positive relationship between the two parameters.

The Role of Hip Arthroscopy in Investigating and Managing the Painful Hip Resurfacing Arthroplasty

To determine the safety and efficacy of hip arthroscopy performed in the peripheral compartment as a diagnostic and therapeutic treatment option for patients with hip pain after hip resurfacing surgery. Indications for hip arthroscopy after hip resurfacing included patients with a symptomatic hip-resurfaced arthroplasties who did not respond to nonoperative treatment. Patients who underwent a hip arthroscopy after a painful hip resurfacing were included with a minimum of 1 year follow-up. Subgroup analysis was performed according to whether an established diagnosis was made before arthroscopic intervention or not. Subjective measures were based on Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, and results were calculated and analyzed. We included 68 patients (26 male [38%] and 42 female [62%]) who underwent subsequent hip arthroscopy from a population of 978 consecutive hip-resurfaced arthroplasties performed between 1999 and 2010. The average age was 58 (range, 37 to 78 years). The mean follow-up after hip arthroscopy was 3.4 years (range, 12 months to 5.8 years). Patients who had an established diagnosis (n= 41) before hip arthroscopy showed statistical improvement in their WOMAC scores (7 to 2, P < .001). Only 3 (7%) of these 41 patients failed and were converted to a total hip replacement (THR); however, patients who did not have an established diagnosis (n= 27) before undergoing hip arthroscopy showed statistical worsening of the WOMAC (15 to 21, P= .002). Ten (37%) of these 27 patients without a diagnosis failed and needed to be converted to a THR. A significant correlation was found between the collections found on ultrasound (psoas bursa and/or in the hip joint) and the need for synovectomy (P= .01). The overall revision rate to THR after hip resurfacing in our group of patients was 1.3% (n= 13). Female patients were more likely to require postresurfacing hip arthroscopy with 42 (60%) female to only 26 (40%) male patients undergoing this procedure. In our study population, 70% (14/21, P < .05) of patients with hip pain caused by severe metal synovial reaction or metal-on-metal reaction were women. A total of 5 (7%) patients had minor-to-mild complications after hip arthroscopy. Hip arthroscopy is a safe surgical treatment option for those patients with a painful hip resurfacing arthroplasty. Having an accurate diagnosis before hip arthroscopy improves the likelihood a good outcome. Level IV - therapeutic case series.

Black joint and synovia: Histopathological evaluation of degenerative joint disease due to Ochronosis

IntroductionOchronotic arthropathy is a rapidly progressive and disabling arthropathy predominantly encountered after the fifth decade of life, caused by homogentisate1,2 dioxygenase enzyme deficiency. As it is rare disease, the literature on histological findings is fragmented. Materials and methodsWe retrospectively re-evaluated histopathological findings in resection and/or curettage materials (5 hip joint, 4 knee joint, one hip joint synovium, one intervertebral disk and one paravertebral disk tissue) of seven ochronosis cases diagnosed between 1995 and 2013 in a single center. ResultsNecrotic brown chondroid detritus was present in all cases either in synovia or in subchondral area, some of which evoked giant cell reaction. Notably, brown pigmentation was prominent in upper middle parts of the articular cartilage but not that prominent in superficial parts and in osteochondral junction, almost stopping at the tide mark. Pigmentation was observed both in extracellular matrix and in cytoplasm either in granular or homogeneous fashion. Depositions were less prominent in osteophytic processes, regenerated cartilaginous areas and loose bodies. Almost all cases showed synovial detritic and inflammatory reaction, fibrillation, eburnation, and subchondral sclerosis. Disk degeneration and findings of ligament rupture were also observed. ConclusionsHistopathological diagnosis of ochronosis is not complicated given the unique “black coloring” of the affected tissues and it can easily be differentiated from other causes of detritic synovitis both clinically and histopathologically. However, there is no definitive cure for today and the reasons for late onset of arthropathy in disease course, and the mechanisms of tissue reaction to fragmented detritus remain elusive.

Identification of normal and pathological posterior inter-malleolar ligament with dedicated high-field vs low-field MRI. A pilot study

the aim of the study was to determine an objective measure of detection of posterior inter-malleolar ligament (PIML) through a magnetic resonance (MRI) of the ankle with two dedicated scanners: high-field (1-Tesla: HMF) and low-field (0.2-Tesla: LMF). two-hundred subjects were randomly recruited for the study and then divided in two groups (HMF and LMF). We retrospectively evaluated the MRI of the ankle in the two groups of patients. PIML evaluation was performed globally and separately using different scan planes. in HMF and LMF, the PIML was identified respectively in 55 and 11% of cases. PIML was classified as "indeterminate" in 28 and 57% of patients, and "absent" in 17 and 32% of patients. In HMF and LMF the isolated evaluation on the coronal, axial and sagittal planes allowed PIML identification respectively in 100 and 100%, 67.27 and 45.45%, 45.45 and 12.4% of cases. In 5 cases (4/5 of HMF) we also observed a posterior ankle impingement syndrome (PAIS) determined by the PIML, with ligament changes (5/5) and associated synovial reactions (1/5), and an arthroscopic confirmation was obtained in 3/5 cases. the presence of the PIML seems to be a possible cause of PAIS and the use of a high-field MR scanner seems optimal for its identification.

Early Response of Mouse Joint Tissue to Noninvasive Knee Injury Suggests Treatment Targets

Joint trauma can lead to a spectrum of acute lesions, including cartilage degradation, ligament or meniscus tears, and synovitis, all potentially associated with osteoarthritis (OA). This study was undertaken to generate and validate a murine model of knee joint trauma following noninvasive controlled injurious compression in vivo. The right knees of 8-week-old mice were placed in a hyperflexed position and subjected to compressive joint loading at 1 of 3 peak forces (3N, 6N, or 9N) for 60 cycles in a single loading period and harvested on days 5, 9, and 14 after loading (n = 3-5 for each time point and for each loading). The left knees were not loaded and were used as the contralateral control. Histologic, immunohistochemical, and enzyme-linked immunosorbent assay analyses were performed to evaluate acute pathologic features in chondrocyte viability, cartilage matrix metabolism, synovial reaction, and serum cartilage oligomeric matrix protein (COMP) levels. Acute joint pathology was associated with increased injurious loads. All loading regimens induced chondrocyte apoptosis, cartilage matrix degradation, disruption of cartilage collagen fibril arrangement, and increased levels of serum COMP. We also observed that 6N loading induced mild synovitis by day 5, whereas at 9N, with tearing of the anterior cruciate ligament, severe posttraumatic synovitis and ectopic cartilage formation were observed. We have established a murine model of knee joint trauma with different degrees of overloading in vivo. Our results suggest that immediate therapies particularly targeted to apoptosis and synovial cell proliferation could affect the acute posttraumatic reaction to potentially limit chronic consequences and OA.

The inhibition of subchondral bone lesions significantly reversed the weight-bearing deficit and the overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn in the monosodium iodoacetate induced model of osteoarthritis pain.

BackgroundChronic pain is the most prominent and disabling symptom of osteoarthritis (OA). Clinical data suggest that subchondral bone lesions contribute to the occurrence of joint pain. The present study investigated the effect of the inhibition of subchondral bone lesions on joint pain.MethodsOsteoarthritic pain was induced by an injection of monosodium iodoacetate (MIA) into the rat knee joint. Zoledronic acid (ZOL), a third generation of bisphosphonate, was used to inhibit subchondral bone lesions. Joint histomorphology was evaluated using X-ray micro computed tomography scanning and hematoxylin-eosin staining. The activity of osteoclast in subchondral bone was evaluated using tartrate-resistant acid phosphatase staining. Joint pain was evaluated using weight-bearing asymmetry, the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG), and spinal glial activation status using glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) immunofluorescence. Afferent neurons in the DRGs that innervated the joints were identified using retrograde fluorogold labeling.ResultsMIA injections induced significant histomorphological alterations and joint pain. The inhibition of subchondral bone lesions by ZOL significantly reduced the MIA-induced weight-bearing deficit and overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn at 3 and 6 weeks after MIA injection; however, joint swelling and synovial reaction were unaffected.ConclusionsThe inhibition of subchondral bone lesions alleviated joint pain. Subchondral bone lesions should be a key target in the management of osteoarthritic joint pain.

Mixed Type I and Type II Collagen Scaffold for Cartilage Repair: Ultrastructural Study of Synovial Membrane Response and Healing Potential versus Microfractures (A Pilot Study)

The association between microfracture of the subchondral plate and a coverage scaffold has emerged as a promising strategy to treat cartilage lesions in a one-step procedure. Between different types of scaffolds (e.g. collagen, hyaluronic acid, polyglycolic acid) currently studied, type I collagen scaffold is the most used for this purpose, and is currently adopted for humans. The aim of this study was to test a novel scaffold made of mixed type I and II collagen (I-IICS) in order to define the immunological reaction of the synovial tissue and the repair capabilities induced by the collagen membrane when associated with microfracture. Eight New Zealand White rabbits, aged 180 days, were operated on bilaterally on the medial femoral condyle. A circular cartilage lesion was performed up to the calcified layer of the medial femoral condyle, and the centre of the lesion was microfractured. Randomly, one of the two lesions was covered with the I-IICS (treated), and the other was left uncovered (control). The synovial membrane reaction and the quality of the cartilage tissue repair were investigated at 2, 90, 180 and 270 days macroscopically, histomorphologically and ultrastructurally. Expression of tumor necrosis factor-alpha (TNF-alpha) in synovial tissue by immunocytochemistry analyses was also investigated. In the control group, at 2 days gold particles were localized mainly on synoviocyte type A, less on synoviocytes type B and on collagen bundles; in the treated group the reaction is more intense in cells in the matrix, but at 180 days controls and treated joints were very similar. The synovial membranes of the joints receiving the I-IICS did not reveal significant changes compared to the age-matched controls. Signs of inflammation were present at the 90-day time-point, and became less evident at afterwards. The degradation of the scaffolds was already evident at the 90-day time-point. The quality of the cartilage repair of the rabbits treated with the I-IICS was slightly better in 5 cases out of 6 in comparison to the controls. However, a statistically significant difference was not detected (p=0.06). Scaffolds made of mixed type I and II collagen exhibited good biocompatibility properties in vivo and favoured cartilage restoration when associated with microfracture, as shown in this pilot study.

Potential of a 70 kDa IL‐10‐like factor in synovial fluid from rheumatoid arthritis patients to augment superoxide generation by human neutrophils

To elucidate the role of polymorphonuclear leukocytes (PMNs) in joint destruction during the inflammatory process in rheumatoid arthritis (RA) as related to superoxide generation. Superoxide generation by human peripheral PMNs was measured by using a water-soluble formazan dye, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt, under PMN stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP) and cytochalasin B. Factors in synovial fluids (SF) from RA patients that may augment PMN superoxide generation were characterized via high-performance liquid chromatography and isoelectric focusing. The formazan dye allowed measurement of superoxide generated in the xanthine-xanthine oxidase system and by PMNs stimulated by cytochalasin B and fMLP in the presence of the intermediate electron transporter phenazine methosulfate. By using chromatography and electrophoresis, an RA-SF protein with an apparent molecular size of 70kDa and an isoelectric point of 8.3 was isolated and was demonstrated to increase superoxide generation by PMNs. The factor was heat-labile and susceptible to protease treatment. This enhancing activity of the factor was absorbed by human PMNs and was somewhat immunoadsorbed with a specific monoclonal antibody against interleukin (IL)-10. The 70-kDa protein factor in RA-SF increased superoxide generation by human PMNs, which suggests the possibility of its being related to IL-10. This factor may have a pathological role in RA joint destruction caused by PMNs and coinciding with rheumatoid inflammation, which suggests that PMNs, via superoxide generation, play an important role in RA joint destruction. IL-10 therefore likely has biological activity toward PMNs during synovial inflammatory chain reactions in RA.

Commentary on an Article by Marianna S. Thomas, FRCR, et al.: “Imaging Metal-on-Metal Hip Replacements: The Norwich Experience”

The article by Thomas et al. [1] is an important review of the vast experience of the radiologists and surgeons from Norwich and adds to the existing fund of knowledge that we have about adverse reactions surrounding metal on metal arthroplasties. As noted by the investigators, adverse reaction to metal debris is not uncommonly found in asymptomatic individuals, in the absence of subjective clinical symptoms such as pain and gait alteration. Serum ion levels have been demonstrated to be insufficient markers by which to monitor synovial reactions to arthroplasty. MRI, using artifact reduction protocols, has proven efficacious in diagnosing adverse reactions to implants, thereby allowing clinicians and orthopedic surgeons to appropriately direct management, including potential revision. An important finding from the Thomas study is that while severe early adverse tissue reactions are associated with significant morbidity, mild synovial expansions may be stable for years, as assessed by their longitudinal assessment of these patients. The findings noted in the recent review presented during the 2013 Freiberger Lecture by Dr. Toms are not dissimilar from the findings of our own MRI laboratory and clinical collaborators. In a recent study of 74 hips in 69 patients with metal on metal resurfacing arthroplasties, both symptomatic and asymptomatic patients were studied, and the magnitude of abnormal synovial response was similar in both the symptomatic and asymptomatic cohorts. However, in the subgroup of patients who underwent revision, the mean volume of synovitis in patients who had an adverse tissue reaction confirmed at revision was higher [2]. In a recently published paper, our group has found that a collection of MR parameters had 90% sensitivity and 86% specificity for determining an adverse histologic score (based on retrieval specimens). In predicting intraoperative damage, these imaging findings had 94% sensitivity and 87% specificity [3]. Our group has found the use of a prototype pulse sequence, developed in collaboration with GE Healthcare, entitled Multi-Acquisition Variable Resonance Image Combination, to be efficacious, particularly in the metal on metal cohorts, as well as in discerning adverse tissue reaction around the trunnion or modular stems in nonmetal implants. A recent study in adverse tissue reactions secondary to tribocorrosion has demonstrated that both synovial thickness and the presence of more solid components highly correlate to adverse tissue reactions confirmed at revision surgery. Thus, the findings in the presented study by Dr. Tom's group, as well as the work being done at our own institution, confirm that MRI is the most useful way by which to detect abnormal synovial response to implants. Radiographic assessment, clinical symptoms, and serum ion levels alone do not predict the presence and extent of adverse tissue reaction. Further longitudinal assessment of these cohorts will be necessary in order to develop predictive models of time to revision, based on a certain magnitude of synovial load or maximum synovial thickness.

Magnetic Resonance Imaging Findings in Symptomatic Versus Asymptomatic Subjects Following Metal-on-Metal Hip Resurfacing Arthroplasty

Although pseudotumors have been reported at the sites of well-functioning and painful metal-on-metal hip prostheses, there are no objective data on the magnitude of the adverse reaction. This observational study was performed to investigate the ability of modified magnetic resonance imaging (MRI) to detect and quantify adverse synovial responses in symptomatic and asymptomatic subjects following metal-on-metal hip resurfacing. We hypothesized that the magnitude of the synovial reactions would be greater in symptomatic patients. Sixty-nine patients (seventy-four hips) with hip resurfacing were divided into three groups: asymptomatic (twenty-two hips), symptomatic with a mechanical cause (twenty), and unexplained pain (thirty-two). The volume of synovitis was calculated on MRI for all patients. Synovitis was detected in fifteen asymptomatic hips (68%), fifteen (75%) with symptoms with a mechanical causes, and twenty-five (78%) with unexplained pain. The mean volume (and standard deviation) of the synovitis in these groups was 5 ± 7 cm³, 10 ± 16 cm³, and 31 ± 47 cm³, respectively. The coefficient of repeatability between the examiners was 1.8 cm³ for measurement of synovitis. Of the thirteen subjects with revision arthroplasty, six had an adverse local tissue reaction. This subgroup had the highest volumes of synovitis on MRI. An adverse synovial reaction was detected on MRI in both symptomatic and asymptomatic subjects. We found a larger volume of synovitis in symptomatic patients; this increase reached significance only in the group with an adverse local tissue reaction. Synovial volume on MRI may be a valuable marker in the longitudinal assessment of asymptomatic patients with a metal-on-metal hip resurfacing and in identifying patients with adverse local tissue reaction.