Head Injury Assessment in the Elite Level Rugby Union in Japan: Review of 3 Seasons.

Head Injury Assessment (HIA) is the screening tool for head injury during a rugby game. The purpose of this study was to investigate the epidemiology of HIA in the Japan Rugby Top League (JRTL). The incidences of HIA, defined concussion (per 1,000 player-hours) and repeated concussions were evaluated in three seasons (2016-17, 2017-18, 2018-19; total 360 games). The HIA incidence rates were 12.7 (95% confidence interval 9.5-15.9), 20.8 (16.8-24.9), and 25.0 (20.5-29.5) in each season. HIA-1 criteria 2, which is applied for suspected concussion cases, was performed for 46 cases in the 2016-17 season, 81 cases in the 2017-18 season, and 88 cases in the 2018-19 season. The concussion incidence rates were significantly greater in the 2017-18 season (9.6/1000 player-hours, 95% confidence interval 6.8-12.4) and the 2018-19 season (14.4, 11-17.8) compared to the 2016-17 season (4.8, 2.8-6.8). The number of repeated concussion cases in the same season was 1 in the 2016-17 season and 4 in both the 2017-18 and 2018-19 seasons. This study confirmed significantly higher HIA and concussion incidence rates over time. Although the HIA system might have been established in the three seasons in JRTL, comprehensive management needs to be improved to prevent repeated concussions.

Hamstring strains in professional rugby players result in increased fascial stiffness without muscle quality changes as assessed using shear wave elastography.

INTRODUCTION: Hamstring strain injury is common among sports injuries. A previous history of this injury is considered a strong predictor of recurrent hamstring strain injury. Fascial tissue reportedly becomes stiffer after hamstring strain injury. However, the association between fascial stiffness and previous hamstring strain injury has not been investigated in clinical studies. We aimed to determine whether a previous history of hamstring strain injury affects fascial tissue and muscle tissues using shear wave elastography. METHOD: In eleven male professional rugby players, the stiffness as a shear modulus (kPa) of fascial tissue and muscle was measured on the specific injured area measured by magnetic resonance imaging (MRI) at resting position by using shear wave elastography. The side-to-side differences between the injured and the uninjured side were analyzed. The length and area of the muscle scar tissue were evaluated by MRI in relation to fascial stiffness. RESULTS: The shear elastic modulus of fascia was stiffer in the injured vs. the uninjured side; however, no difference was observed in the muscle. No significant relationship was detected between the length and area of the muscle scar tissue (all P > 0.05). DISCUSSION: Rugby players with a previous history of hamstring strain injury exhibited passive stiffness of fascial tissues in the injured leg, regardless of the length or area of the muscle scar tissue. However, the passive stiffness of muscles was same between the injured and the uninjured leg. CONCLUSION: The results can be beneficial to consider future risk for hamstring strain injuries.

Does the duration to bipolar hip arthroplasty for femoral neck fracture influence on postoperative muscular strength?

BACKGROUND: The primary purpose of this study was to compare the postoperative muscular strength and functional performance between early versus late bipolar hip arthroplasty (BHA) intervention for femoral neck fracture classified by the duration from the onset to surgery. METHODS: Twenty-one patients who could walk at 12 months or more after BHA were enrolled into this study. We examined the muscular strength of hip flexion, extension, abduction, and knee extension of these patients. Time of one-leg standing, timed up and go test, pain grade by visual analog scale, and Barthel index were also evaluated as functional indices. We classified these patients into two groups by the duration from the onset to surgery, namely: within 3 days until BHA (early OP) and more than 4 days (late OP) to compare these indices at the latest follow-up. RESULTS: The mean days until operation were 2.3 days in the early-OP group and 5.9 days in the late-OP group, showing a significant difference between the two groups. Muscular strength and other functional indices were also found to have no significant differences between these two groups. CONCLUSION: Our study suggests that the delay to operate might not severely compromise the muscular strength around the hip joint for least 1.5 years among ambulatory patients.

Innovative technique of minimally invasive closed reduction for impacted femoral neck fractures (MICRIF).

The moment arm of gluteus medius proportionated to distance from femoral head tends to be decreased postoperatively in valgus-impacted femoral neck fractures treated by in situ internal fixation. The aim of this article is to introduce a new gentle technique to correct the deformity. The innovative technique of Minimally Invasive Closed Reduction for Impacted Femoral neck fractures (MICRIF) mainly focused to disimpact valgus neck fractures into anatomical position. Patients were positioned on the fracture table to fix the hip joint in abduction and internal rotation. A 2.4-mm diameter Kirschner wire was inserted a few centimetres outside the iliac crest piercing the acetabular beak to enter the femoral head, followed by repositioning of the lower extremity from abduction into neutral. This method provides satisfactory anatomical reduction. Thereafter, a surgical implant was applied to osteosynthesize the reduced fracture. This simple technique effectively provides anatomical reduction in valgus impacted femoral neck fracture.

Dynamic finite element analysis of implants for femoral neck fractures simulating walking.

BACKGROUND: To examine postoperative complications for osteosynthesizing femoral neck fractures (Pauwels III), biomechanical analysis should be conducted under dynamic conditions simulating for walking, not static conditions. Among the two main aims of this study, one is to pioneer the technique of dynamic finite element (FE) analysis, and the other is to compare stress distribution between two implants during walking. MATERIALS AND METHODS: First, we performed an inverse dynamic analysis with optimization method using a musculoskeletal model to calculate the inter-segmental and muscular forces during walking. Second, three FE models were prepared: (I) intact hip joint, (II) fractures treated with two Hansson pins (HP), and (III) fractures with Dual SC Screws (DSCS) maintaining an angular stability. The direction and magnitude of the loadings varied continuously. Stress distribution during the walking was evaluated by using a dynamic explicit method. We examined the time-dependent von Mises stresses at two representative spots: medial cortex at the femoral neck fracture site and lateral pin (presumed) insertion holes. RESULTS: In general, stress values are always changing during walking cycle. Regarding medial femoral neck cortex at the fracture line, intact model showed almost consistent value. Both HP model and DSCS model amounted the highest around 30 MPa. At lateral holes, highest values were 18.8, 104.0, and 63.1 MPa of intact, HP, and DSCS models, respectively. CONCLUSION: Thus, our analysis simulating the real walking will be useful in evaluating time-varying stress distribution to assess postoperative complication. CLINICAL RELEVANCE: DSCS is expected to be paramount for treatment of unstable femoral neck fractures.

Decreased postoperative gluteus medius muscle cross-sectional area measured by computed tomography scan in patients with intertrochanteric fractures nailing.

BACKGROUND: In patients with femoral intertrochanteric fractures treated by cephalomedullary (CM) nailing, abduction force reportedly decreased by 25-30% during the postoperative follow-up period. The purpose of the current study is to evaluate the cross-sectional area (CSA) and adipose tissue ratio (ATR) of the gluteus medius muscle on the postoperative computed tomography (CT) view, expecting this graphic study will support clinical results. MATERIALS AND METHODS: A total of 27 patients with femoral intertrochanteric fractures treated by CM femoral nail implants completed the study. The mean age at osteosynthesis was 83 years (range: 72-94 years). The mean postoperative follow-up period was 23 months. The three CT axial slice views were defined as slices A, B, and C corresponding to proximal, midway, and distal part of gluteus medius, respectively. The CSA and ATR were assessed bilaterally. RESULTS: The mean and standard deviation of CSA values (mm2) between the nonoperated/ operated side were as follows: slice A: 2225.8 ± 621.2/1984.5 ± 425.8; slice B: 2145.1 ± 538.3/1854.9 ± 383.9; and slice C: 1711.0 ± 459.0/1434.5 ± 396.9 ( p < 0.01 in slices A, B, and C). The mean and standard deviation of ATR values (%) from the nonoperative/ operative side were as follows: slice A: 2.8 ± 1.7/5.2 ± 3.5; slice B: 2.7 ± 1.9/4.6 ± 3.2; and slice C: 3.6 ± 3.0/4.8 ± 3.2 ( p < 0.01 in slices A and B and p < 0.05 in slice C). CONCLUSION: Our image findings documented that gluteus medius is significantly changed in CSA and ATR. The damage possibly triggers decrease in muscular strength of hip abduction in the postoperative follow-up period. This measurement is objective, and needed no patient's endurance and cooperation.

Comparison of Post-Operative Muscular Strength Between Gamma Nailing and Hemiarthroplasty System in Femoral Intertrochanteric Fractures.

BACKGROUND: The current study focuses on the comparison of postoperative muscular strength around the hip joint of patients with femoral intertrochanteric fractures treated either by cephalo-medullary (CM) nailing or a new bipolar hip prosthesis (BHP), an especially attached device to secure displaced greater trochanteric fragment. METHODS: Twenty patients treated with CM nailing were age- and sex- matched with a control group of 20 patients treated with BHP. Maximum isometric forces at the bilateral hip joint were measured during the follow up period. Means of 3 measurements were represented. RESULTS: The mean and standard deviation values (kg) of muscle strength at the non-operative/ operative side in the CM nailing group were as follows: flexion strength 9.5±4.7/8.5±4.9 (P=0.06), extension strength 6.2±3.5/5.5±3.7 (P=0.08), abduction strength at 0 degrees 7.7±3.5/6.2±2.8 (p=0.002), abduction strength at 10 degrees 5.5±2.0/4.2±2.0 (p=0.001). In the BHP group, mean and standard deviation values of muscle strength at the non-operative/ operative side were as follows: flexion strength 6.5±2.8/6.0±3.4 (P=0.08), extension strength 4.4±0.9/4.4±0.6 (P=0.83), abduction strength at 0 degrees 5.1±1.9/5.0±1.6 (p=0.12), and that at 10 degrees 4.7±1.4/4.6±1.3 (p=0.10). CONCLUSION: Our results demonstrate that CM nailing may cause a 25-30% decrease in postoperative muscle strength around the hip joint, particularly during hip abduction. With the new BHP, greater trochanter reduction is achieved allowing early weight bearing and maintaining strength in abduction. Surgeons should consider postoperative muscular strength as one of the necessary factors for selection of the appropriate surgical procedure. LEVEL OF EVIDENCE: Therapeutic Level III.

Diminished abductor muscular strength in patients with valgus-impacted femoral neck fractures treated by internal fixation: Clinical study and biomechanical considerations.

BACKGROUND: Valgus-impacted femoral neck fractures treated with internal fixation occasionally result in unsatisfactory postoperative locomotive function, partially due to muscle shortening and a decrease in the moment arm. This study quantifies the degree of diminished abduction strength both clinically and biomechanically. METHODS: Fifteen patients were enrolled in this study. Twelve patients with fracture healed in valgus-impacted position were further evaluated. Muscular strength around hip was examined, and values between the nonoperated and operated side were compared and analyzed. For the biomechanical study, two three-dimensional models were prepared: model I (control model without displacement) and model II (simulated malunion of a 15° valgus-impacted fracture). Two sets of hip flexion angles in each of the models were simulated with flexion angles of 0° and 23°. RESULTS: Mean and standard deviation values for muscle strength from the nonoperative/operative side among the valgus group are as follows: flexion strength was 9.2 ± 4.0/9.2 ± 3.2, extension strength was 5.8 ± 2.8/6.1 ± 3.2, abduction strength at 0° was 9.1 ± 3.7/7.4 ± 3.6, abduction strength at 10° was 6.7 ± 3.0/5.5 ± 2.2, and knee extension strength was 15.3 ± 6.2/15.1 ± 6.0 (kgf). When comparing values between the nonoperative and operative sides, statistical significance was only observed in abduction strength ( p < 0.01). The biomechanical models prove that valgus impaction decreases the moment arm by approximately 10% at both flexion angle. CONCLUSIONS: A significant decrease in abductor strength at 0° and 10° was observed in the valgus-healed group. This may be related to a decrease in the moment arm. Further research should be done to define the acceptable limit of deformity for the satisfactory postoperative functioning.

Functional MRI of the Reserpine-Induced Putative Rat Model of Fibromyalgia Reveals Discriminatory Patterns of Functional Augmentation to Acute Nociceptive Stimuli.

Functional neuroimaging, applied to pre-clinical models of chronic pain, offers unique advantages in the drive to discover new treatments for this prevalent and oppressive condition. The high spatial and temporal resolution of fMRI affords detailed mapping of regional pharmacodynamics that underlie mechanisms of pain suppression by new analgesics. Despite evidence supporting the translational relevance of this approach, relatively few studies have investigated fMRI abnormalities in rodent models of chronic pain. In this study, we used fMRI to map the BOLD response in a recently developed putative rat model of fibromyalgia to innocuous and acute nociceptive stimuli by applying a step-wise graded electrical forepaw stimulation paradigm, with comparison to healthy controls. We observed discriminatory functional signatures (p < 0.001) to 2 mA electrical forepaw stimulation, found to be innocuous in the control group. As such, this translational approach provides sensitive and quantitative neural correlates of the underlying chronic disease. The regional patterns of functional augmentation were found to be concordant with previous studies of nociception in the anaesthetised rat brain, supporting the specificity of this approach in the study of altered central pain processing in reserpine induced myalgia. The methodology introduced in this work represents a novel platform for emerging treatment evaluation in highly experimentally controlled conditions.

Spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain respond differently to drugs with different mechanisms of action.

Given that patients with neuropathic pain suffer a mixture of spontaneous and evoked pain symptoms, we assessed the effects of drugs with different mechanism of action on spontaneous and evoked pain-associated behaviors in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Frequent aberrant limb movement on the operated side was measured to assess spontaneous pain-associated behavior, and mechanical allodynia and thermal hyperalgesia were evaluated to assess evoked pain-associated behaviors. These three types of behavior were assessed after administration of the following drugs: pregabalin (α2δ-subunit ligand), morphine (µ-opioid receptor agonist), perampanel (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] receptor antagonist), clonidine, dexmedetomidine (α2-adrenoceptor agonists), and diclofenac (non-steroidal anti-inflammatory drug [NSAID]). Pregabalin at an oral dose of 10 or 30mg/kg significantly alleviated frequent aberrant limb movement and mechanical allodynia, but not thermal hyperalgesia. Morphine at a subcutaneous dose of 1 or 3mg/kg significantly improved all three types of behavior. Perampanel at an oral dose of 1mg/kg attenuated only frequent aberrant limb movement. Intraperitoneal administration of clonidine (0.01 or 0.03mg/kg) and dexmedetomidine (0.03mg/kg) significantly improved all three types of behavior, while diclofenac did not relieve any of the behaviors. Pregabalin, clonidine, and dexmedetomidine significantly decreased motor performance at doses close to analgesic doses in the rotarod test. The present study demonstrates that responses to spontaneous and evoked pain symptoms in neuropathic pain condition differ depending on a drug's mechanism of action. The selection and application of drugs according to the specific symptoms would be considered for the medication of patients with neuropathic pain.

Biomechanical Study Using the Finite Element Method of Internal Fixation in Pauwels Type III Vertical Femoral Neck Fractures.

BACKGROUND: Several factors are known to influence osseous union of femoral neck fractures. Numerous clinical studies have reported different results, hence with different recommendations regarding treatment of Pauwels III fractures: femoral neck fractures with a more vertically oriented fracture line. The current study aimed to analyze biomechanically whether this fracture poses a higher risk of nonunion. OBJECTIVES: To analyze the influence of one designated factor, authors believe that a computerized fracture model, using a finite element Finite Element Method (FEM), may be essential to negate the influence of other factors. The current study aimed to investigate a single factor, i.e. orientation of the fracture line toward a horizontal line, represented by Pauwels classification. It was hypothesized that a model with a vertically oriented fracture line maintaining parity of all other related factors has a higher stress at the fracture site, which would delay fracture healing. This result can be applicable to other types of pinning. PATIENTS AND METHODS: The finite element models were constructed from computed tomography data of the femur. Three fracture models, treated with pinning, were constructed based on Pauwels classification: Type I, 30° between the fracture line and a horizontal line; Type II, 50°; and Type III, 70°. All other factors were matched between the models. The Von Mises stress and principal stress distribution were examined along with the fracture line in each model. RESULTS: The peak Von Mises stresses at the medial femoral neck of the fracture site were 35, 50 and 130 MPa in Pauwels type I, II, and III fractures, respectively. Additionally, the peak Von Mises stresses along with the fracture site at the lateral femoral neck were 140, 16, and 8 MPa in Pauwels type I, II, and III fractures, respectively. The principal stress on the medial femoral neck in Pauwels type III fracture was identified as a traction stress, whereas the principal stress on the lateral femoral neck in Pauwels type I fracture was a compression stress. CONCLUSIONS: The most relevant finding was that hook pinning in Pauwels type III fracture may result in delayed union or nonunion due to significantly increased stress of a traction force at the fracture site that works to displace the fracture. However, in a Pauwels type I fracture, increased compression stress contributes to stabilize it. Surgeons are recommended not to treat Pauwels type III femoral neck fractures by pinning.

Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts.

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TNF-like ligand 1A (TL1A). We previously reported that TNFα-induced DcR3 overexpression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) protects cells from Fas-induced apoptosis. Previous studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages into osteoclasts. Furthermore, we reported that DcR3 induces very late antigen-4 (VLA--4) expression in THP-1 macrophages, inhibiting cycloheximide-induced apoptosis and that DcR3 binds to membrane-bound TL1A expressed on RA-FLS, resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. In the current study, we used cDNA microarray to search for genes in RA-FLS whose expression was regulated by the ligation of DcR3. The experiments revealed the expression profiles of genes in RA-FLS regulated by DcR3. The profiles showed that among the 100 genes most significantly regulated by DcR3, 45 were upregulated and 55 were downregulated. The upregulated genes were associated with protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic processes, cell membrane, nucleotide binding and glycosylation. The downregulated genes were associated with transcription regulator activity, RNA biosynthetic processes, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic processes, mitochondrion, ion transport, nucleotide binding and cell fractionation. Further study of the genes detected in the current study may provide insight into the pathogenesis and treatment of rheumatoid arthritis by DcR3-TL1A signaling.

A new treatment for avulsion fracture of the calcaneus using an Ilizarov external fixator.

INTRODUCTION: In the treatment of avulsion fractures of the posterior calcaneal tuberosity, open reduction and internal fixation are prone to several complications. We describe a new treatment using an Ilizarov external fixator, which can minimise the complications and achieve sufficient stability of the displaced fragment. CASE PRESENTATION: A 55-year-old woman sustained an avulsion fracture of the calcaneus. Examination revealed the development of bruising with extremely taut skin over the posterior prominence of the displaced bone. Radiographs demonstrated grossly proximal displacement of the tuberosity fragment. Surgery was exclusively percutaneous using an Ilizarov external fixator. The displaced fragment was adequately reduced and stabilised. Progressive weight bearing in the equinus position was initiated at the third week after surgery and the external fixator was removed at the seventh week. There was no skin necrosis or loss of reduction while the fixator was maintained. Postoperative follow-up for 2 years revealed full recovery. DISCUSSION: Major postoperative complications after conventional open reduction and internal fixation include skin necrosis, skin irritation by metal implants and re-displacement of the reduced fragment. Our method of using an external fixator may decrease the incidence of these three complications. Skin incision and the risk of skin necrosis are inevitable during internal fixation. On the other hand, the use of an external fixator reduces or eliminates skin necrosis, as it is applied percutaneously for reduction and stabilisation of the fragment. External fixation is mostly recommended in cases of poor vascularity or bruising. In addition, skin irritation can be avoided upon removal of the external fixator. Re-displacement occurs occasionally as a serious complication in lag screw fixation, particularly in cases with poor purchase of the osteoporotic bone. Tension band wiring and application of an Ilizarov external fixator in avulsion fractures of the calcaneus can neutralise tension on the Achilles tendon during the healing process. Thus, both these methods are believed to provide sufficient mechanical stability to fix the fragment. CONCLUSION: This new method, involving application of an Ilizarov external fixator, is recommended when the avulsion fragment is large enough to accommodate Ilizarov wires, especially in cases of circulatory problems or bruising.

A case of the geniculate artery pseudoaneurysm after total knee arthroplasty: search for preventive measures by evaluation of arterial anatomy of cadaver knees.

This article presents an 80-year-old man with pseudoaneurysm of the inferolateral geniculate artery after total knee arthroplasty (TKA). The aim is to report this case and review possible preventive methods of pseudoaneurysm formation after TKA by investigating the relationship between knee arterial anatomy and the TKA procedure. Cadaveric evaluation demonstrates that the superomedial and inferomedial geniculate arteries are difficult to visualize. The anatomical position of the inferolateral artery makes it vulnerable to the surgical procedure during cutting of the tibia or while retracting soft tissue from the tibial edge, especially with minimal invasive surgery. In conclusion, careful subperiosteal release around the geniculate arteries is recommended. However, early recognition of pseudoaneurysm formation is even more essential than prevention.

Decreasing Complications of Quadricepsplasty for Knee Contracture after Femoral Fracture Treatment with an External Fixator: Report of Four Cases.

INTRODUCTION: In performing quadricepsplasty for contracture that develops after application of an external fixator for femoral fractures, surgeons must be aware of the potential risk for re-fracture and pin-related problems. The purpose of this report is to highlight these not well-detailed complications and to discuss specific findings and treatment suggestions. CASE SERIES: 4 men (mean age, 40 years) presenting with secondary to contracture that developed after application of an external fixator for femoral fractures were included in this study. The radiographs showed union across the fracture site however two of these patients couldn't stand on one leg raising suspicion about the union status. A computed tomographic image indeed demonstrated limited continuity of the cortex. Bone grafting was performed prior to quadricepsplasty. The mean extension and flexion before the quadricepsplasty were 0° and 57°, respectively. At the final follow-up examination, the mean active flexion of the knee had increased to 98°. RESULTS: The incidence of re-fracture during and after quadricepsplasty has been reported to be between 10 and 25%. There are 2 preoperative features that may mislead surgeons into believing that complete union of the fractures has been attained: one is the patient's ability to stand on a single leg, and the other is the fact that plain radiographs may lend themselves to different interpretations. In such cases, computed tomography will provide evidence of the continuity of the cortical bone. Bone grafting in 2 of our patients is thought to have prevented the postoperative complications of re-fracture. Complications at pin sites induce contracture at surrounding structures. When extreme tightness of the skin is noted, a tension-releasing procedure such as a skin graft should be performed. CONCLUSION: In conclusion, re-fracture or pin-site contracture should be carefully managed before quadricepsplasty, because the patients who need a lengthy application of an external fixator experience greater difficulty in bone healing and have more soft tissue damage.

Different pathophysiology underlying animal models of fibromyalgia and neuropathic pain: comparison of reserpine-induced myalgia and chronic constriction injury rats.

The reserpine-induced myalgia (RIM) rat manifests fibromyalgia-like chronic pain symptoms. The present study explored the pathophysiology underlying the pain symptoms in the RIM rat and the chronic constriction injury (CCI) rat, an animal model of neuropathic pain as a reference. Nerve tissue samples were collected from the nociception-tested animals for pathological examinations. Additionally, the therapeutic efficacy of a sodium channel blocker mexiletine was assessed in both rats. A slight vacuolization in the substantia nigra (SN) occurred in some of the RIM rats without any other histopathological changes in the brain or peripheral neurons. All the RIM rats, with or without vacuolization, showed hypersensitivity to tactile, muscle pressure, and cold stimuli. In the CCI rat, neurodegenerative changes were apparent in the sciatic nerve and the spinal cord only. CCI rats displayed muscle hyperalgesia in addition to tactile and cold allodynia. Pharmacotherapy with mexiletine did not attenuate the pain in the RIM rat, although it was effective in the CCI rat. Taken together, it is not likely that pain symptoms in RIM rats are caused by degenerative changes at the level of primary afferents and spinal cord, as is the case for CCI rats. The significance of the vacuolization in the SN is less clear at present because of the minor extent of the change and the lack of correlation with nociceptive sensitivity. The pain symptoms in RIM rats could be associated with dysfunction of biogenic amines-mediated CNS pain control even without apparent pathologies in the nervous system.

DcR3-TL1A signalling inhibits cytokine-induced proliferation of rheumatoid synovial fibroblasts.

Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TL1A. We previously reported that TNFα-induced DcR3 overexpression in rheumatoid synovial fibroblasts (RA-FLS) protects the cells from Fas-induced apoptosis and that DcR3 induces VLA-4 expression in THP-1 macrophages to inhibit cycloheximide-induced apoptosis. Meanwhile, recent studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages to osteoclasts. Therefore, in the present study, we analyzed the direct effects of DcR3 as a ligand in RA-FLS. The experiments showed that DcR3 binds to TL1A expressed in RA-FLS resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. DcR3-TL1A signalling may be involved in the pathogenesis of rheumatoid arthritis (RA).

Decoy receptor 3 is highly expressed in patients with rheumatoid arthritis.

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a soluble receptor that binds to the TNF family including Fas ligand (Fas-L), LIGHT, and TL1A. DcR3 is mostly expressed in tumor cells and competitively inhibits the TNF family. We previously demonstrated that overexpressed DcR3 in rheumatoid synovial cells protects the cells from apoptosis in vitro. The objective of the study was to investigate DcR3 expression in serum and joint fluids of patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to analyze the correlations with disease activities and TNFalpha expression. Sera and joint fluids were collected from patients with RA and OA. Expression of DcR3 in sera and joint fluids was measured by ELISA. The concentration of DcR3 in sera and joint fluids of RA patients was significantly higher than that in sera and joint fluids of OA patients. A correlation between serum DcR3 concentration and disease activity was not observed, but the serum DcR3 concentration was strongly correlated with the TNFalpha concentration. DcR3 was highly expressed in serum and joint fluids of RA patients.

DcR3 protects THP-1 macrophages from apoptosis by increasing integrin alpha4.

In order to analyze the function of DcR3 for the regulation of cell adhesion and apoptosis in macrophages, we investigated the expression of decoy receptor 3 (DcR3) in THP-1 monocytes/macrophages. DcR3 was expressed in THP-1 and increased by phorbol 12-myristate 13-acetate (PMA). The formation of macrophage aggregates was observed when THP-1 cells were differentiated by PMA or stimulated with DcR3-Fc. Undifferentiated THP-1 cells were also induced to form aggregates by DcR3-Fc. The expression of integrin alpha4 was significantly increased by DcR3-Fc. CHX-induced apoptosis in THP-1 was inhibited by DcR3-Fc, of which inhibition against CHX-induced apoptosis and aggregate formation were ameliorated by anti-VLA4 antibody. DcR3 may play a significant role in macrophages not only by a decoy receptor but also by increasing alpha4 integrin.