Search

Background The relationship between the femoral component design in total knee arthroplasty (TKA) and the patellofemoral contact force, as well as the soft tissue balance, has not been well reported thus far. Methods Twenty-eight mobile-bearing posterior-stabilized (PS) TKAs using the traditional model (PFC Sigma) and 27 mobile-bearing PS TKAs using the latest model (Attune) were included. Surgeries were performed using the measured resection technique assisted with the computed tomography (CT)-based free-hand navigation system. After all the trial components were placed, patellar contact forces on the medial and lateral sides were measured using two uniaxial ultrathin force transducers with the knee at 0°, 10°, 30°, 60°, 90°, 120°, and 135° of flexion. The joint component gap and the varus ligament balance of the femorotibial joint were also measured. The non-paired Student’s t-test was conducted to compare the values of the two groups. Results The medial patellar contact force was significantly lower for Attune group than for PFC Sigma group at 120° of knee flexion (P = 0.0058). The lateral patellar contact force was also significantly lower for Attune group than PFC Sigma group at 120° and 135° of knee flexion (P = 0.0068 and P = 0.036). The joint component gap, as well as the varus ligament balance, showed no statistically significant difference between the two groups. Conclusions Reduced thickness and width of the anterior flange of the femoral component in the Attune may play a role in low patellar contact force.

Background To improve implant survival through accelerated early bone remodeling during total hip arthroplasty (THA), hydroxyapatite (HA) is widely used as a bioactive coating, which is believed to enhance initial fixation by osseointegration. We aimed to investigate the relationship between stem insertion alignment and postoperative bone mineral density (BMD) changes in patients with full hydroxyapatite-coated (HA) compaction short stem and short tapered-wedge stem. Methods This retrospective cohort study enrolled 115 consecutive patients (115 joints) undergoing THA using the full HA compaction short (n = 59) and short tapered-wedge (n = 56) stems. Stem alignment, including anteversion, valgus, and anterior tilt were measured by a three-dimensional template using computed tomography data. Post-operative peri-prosthetic BMD was measured by dual-energy X-ray absorptiometry. The relationship between stem alignment and BMD changes in the stems was analyzed. Results Patterns of peri-prosthetic BMD changes were similar in both groups. Stem insertion alignments of anteversion, valgus, and anterior tilt were different between the two stem types. Stem alignment of valgus and anterior tilt did not affect peri-prosthetic BMD in either of the stem type. An absolute anteversion difference between stem anteversion and original canal anteversion caused significant peri-prosthetic BMD loss in Gruen zones one and seven in the tapered-wedge stem. However, stem alignment of absolute anteversion difference did not affect BMD changes in the HA compaction stem. Conclusions Peri-prosthetic bone remodeling remained unaffected by stem alignment after THA with the new short full HA compaction stem.

Herpes zoster (HZ) is known as a side effect of using biologics in rheumatoid arthritis (RA). Incidence of this side effect may be different depending on genetic factors because susceptibility to HZ infection varies by race. Here, we analyzed the statistical relationships of whole genome single nucleotide polymorphisms (SNPs) with HZ infection in biologics-treated RA patients.The subjects were 321 Japanese female patients (including 56 herpes virus infected patients) of RA using biologics. The relationships of 302,814 SNPs with HZ infection were analyzed using case-control analyses by Fisher’s exact tests. We picked up SNPs (P < 10-8) significantly associated with HZ infection. Then, herpes infection was compared among the genotypes using a multivariate logistic regression analysis adjusted for onset age of RA.Rs10774580 located in 2’-5’-oligoadenylate synthetase like gene (OASL) was significantly associated with herpes virus infection. The minor allele homozygous carrier was positively associated with herpes virus infection in multivariate analysis.We for the first time showed a significant relationship between a genetic factor and HZ infection among RA patients. Rs10774580 may be one of the biomarkers for HZ infection.

Introduction The concept of anatomic restoration has garnered considerable interest in the form of kinematically aligned total knee arthroplasty (KA-TKA). KA-TKAs have been reported to reproduce natural alignment and kinematics. However, few randomized controlled trials (RCTs) have compared the biomechanical outcomes and the long-term clinical outcomes of KA-TKA with those of mechanically aligned TKA (MA-TKA). We aim to investigate the long-term clinical and biomechanical effects of KA-TKA and to determine whether KA-TKA or MA-TKA is more appropriate for primary TKA. Methods This trial will compare clinical and biomechanical outcomes of KA-TKA to those of MA-TKA. Two hundred patients will be enrolled in the RCT and randomized into KA-TKA or MA-TKA groups. Both the groups will be evaluated 1 week before the operation, on the day of the operation, 6 months after the operation, and 1, 5, and 10 years after the operation. The primary outcome is the difference between preoperative and 1-year postoperative functional activity scores of the 2011 Knee Society Score (2011 KSS) in both groups as well as the differences between the scores of both groups. The secondary outcomes will include differences in symptom, satisfaction, and expectation scores of the 2011 KSS, intraoperative kinematics evaluation, postoperative clinical outcomes and complications, pre- and postoperative gait analyses and radiograph evaluations between both KA-TKA and MA-TKA.

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder whose progression is modulated by fibroblast-like synoviocytes (FLSs). Cyclin-dependent kinase (CDK) inhibitor 1 (p21) regulates the activation of other CDKs, and we recently reported that p21 deficiency induces susceptibility to osteoarthritis. Here, we focused on joint inflammation to determine the mechanisms associated with p21 function in synovial and cartilage tissues in RA.Methods: p21-knockout (p21-/-) mice and wild-type C57BL/6 (WT p21+/+) mice were used to establish a collagen antibody-induced arthritis (CAIA) model. The severity of arthritis was evaluated visually, and histological and immunohistological analyses performed 7, 14, and 28 days after injection with a cocktail of five monoclonal antibodies that recognize conserved epitopes on various species of type II collagen. The response of p21 siRNA-treated human RA FLSs to IL-1β stimulation was also determined.Results: Arthritis scores were higher in p21-/- mice than those in p21+/+ mice. More severe and prolonged synovitis of the knee joints and earlier loss of staining and cartilage destruction were observed in p21-/- mice than in p21+/+ mice. p21-/- mice expressed higher levels of IL-1β, F4/80, p-IKKα/β, and MMPs in cartilage and synovial tissues at each time point, except for before injection of the monoclonal antibodies, via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased MMP expression and enhanced IKKα/β phosphorylation in human FLSs.Conclusion: p21-deficient CAIA mice are susceptible to alterations in the RA phenotype, including joint cartilage destruction and severe synovitis, via IL-1β-induced inflammation. Therefore, p21 regulation may constitute a possible strategy for RA treatment.

Background Fas ligand (FasL) is a member of tumor necrosis factor superfamily (TNFSF6) and reported to contribute to synovial hyperplasia of rheumatoid arthritis (RA). Apoptosis of RA synovial cells through Fas/FasL pathway was inhibited by pro-inflammatory cytokines present within the synovium [1]. We previously reported that decoy receptor 3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated by TNFα protects the cells from Fas-induced apoptosis [2]. Objectives In this study, we investigated the gene expression profiles regulated by FasL in RA-FLS to reveal how FasL is involved in the pathogenesis of RA. Methods RA-FLS were obtained during total knee replacement surgery from patients with RA. Four individual lines of primary cultured RA-FLS were incubated either with 1000 ng/ml of recombinant human FasL protein or the same volume of phosphate buffered saline as unstimulated control in reduced serum medium for 12h. Gene expressions were detected by microarray assay (Human Genome U133 Plus 2.0, GeneChip® 3’ Expression Array; Thermo Fisher Scientific). Results Microarray data analysis revealed that FasL up-regulated or down-regulated the expression of various genes in RA-FLS. The function of regulated genes included transcriptional activator activity, positive regulation of metabolic process, positive regulation of cellular metabolic process, positive regulation of macromolecule metabolic process, positive regulation of nitrogen compound metabolic process, regulation of phosphorylation, positive regulation of biological process, regulation of phosphate metabolic process, regulation of MAPK cascade, and regulation of multicellular organismal process. The most up-regulated 3 genes by FasL were dual specificity phosphatase 6 (DUSP6), epiregulin (EREG) and interleukin11 (IL-11). The most down-regulated 3 genes by FasL were angiopoietin-like 7 (ANGPTL7), protein inhibitor of activated STAT2 (PIAS2) and growth differentiation factor 5 (GDF5). Conclusion DUSP6 regulates CD4+ T-cell activation and differentiation by inhibiting the T-cell receptor-dependent extracellular signal-regulated kinases 1 and 2 activations [3]. EREG is increased in patients with RA and associated with the development of cytokine-induced arthritis [4]. IL-11 regulates the growth and development of hematopoietic stem cells and decreases the pro-inflammatory cytokines and nitric oxide productions [5]. ANGPTL7 is pro-angiogenic factor [6] and promotes pro-inflammatory responses through the P38 signaling pathway [7]. PIAS proteins inhibit the activated STAT and are involved in the pathogenesis of RA [8]. GDF5 is associated with joint destruction of patients with OA and RA [9]. FasL regulates the expression of various genes in RA-FLS. Therefore, FasL may affect the pathogenesis of RA by regulating gene expressions of these molecules in RA-FLS. References [1] Wakisaka S. et al., Clin Exp Immunol. 1998;114:119-128. [2] Hayashi S. et al., Arthritis Rheum. 2007;56:1067-1074. [3] Bertin S. et al., Mucosal Immunol. 2015;8:505-515. [4] Harada M. et al., J Immunol. 2015;194:1039-1046. [5] Moreland L. et al., Arthritis Res. 2001;3:247-252. [6] Katoh Y, et al., Int J Mol Med. 2006;17:1145-1149. [7] Quian T, et al., Inflammation. 2016;39:974-985. [8] Lao M. et al., J Immunol. 2016;196:596-606. [9] Martinez A. et al., Ann Rheum Dis. 2008;67:1352-1353. Disclosure of Interests None declared

Rheumatoid arthritis (RA) is a common chronic autoimmune disease leading to joint destruction. The aim of the present study was to identify the genomic factors predictive of susceptibility to joint destruction in patients with RA by performing a genome‑wide association study of genetic variants, including single nucleotide polymorphisms (SNPs). The study sample included 228 patients with a diagnosis of RA in the past 5 years. Patients were classified into rapid (total Sharp score/years of RA, ≥50) and slow (total Sharp score/years of RA

BackgroundNovel therapeutic strategies for the healing of nonunion, which has serious effects on the quality of life of patients, are needed. We evaluated the therapeutic effect of local transplantation of human stromal vascular fraction (SVF) cells on fracture healing in a rat non-healing fracture model and compared the effects between freshly isolated (F) and cryopreserved (C)-SVFs.MethodsNon-healing fracture model was induced in the femur of female immunodeficient rats (F344/N Jcl rnu/rnu) with cauterizing periosteum. Immediately after the creation of non-healing fracture, rats received local transplantation of F and C-SVFs suspended in phosphate-buffered saline (PBS) or the same volume of PBS without cells using the same scaffold as a control group. During 8 weeks post-surgery, radiologic, histological, immunohistochemical, and biomechanical analyses were performed to evaluate fracture healing. The comparison of radiological results was performed with a chi-square test, and the multiple comparisons of immunohistochemical, histological, and biomechanical results among groups were made using a one-way analysis of variance. A probability value of 0.05 was considered to denote statistical significance.ResultsAt week 8, in 60% of animals receiving F-SVF cells and in 50% of animals receiving C-SVF cells, the fracture radiologically healed with bone union whereas nonunion was observed in the control group. The healing potential was also confirmed by histological and biomechanical assessments. One of the mechanisms underlying healing involving intrinsic angiogenesis/osteogenesis was enhanced in F- and C-SVF groups compared with that in the control group. Human cell-derived vasculogenesis/osteogenesis, which was also confirmed in an in vitro differentiation assay, was also enhanced in the F- and C-SVF groups compared with that in the control groups and could be another mechanism for healing.ConclusionsSVF cells can enhance bone healing and cryopreserved cells have almost equal potential as fresh cells. SVF cells can be used for improving nonunion bone fracture healing as an alternative to other mesenchymal stem cells and the effect of SVF cells can be maintained under cryopreservation.

Treatment of rheumatoid arthritis (RA) is aimed at long-term remission and inhibition of joint destruction by different biologic drugs. However, the choice of a particular biologic agent based on individual cases of RA remains unestablished. Interleukin-6 (IL-6) inhibitor and tumor necrosis factor (TNF) inhibitor are common biologics used for the treatment of RA. This study aimed to investigate predictive factors for effective selection of tocilizumab (IL-6 inhibitor) and etanercept (TNF inhibitor) in patients with RA. This is a retrospective cohort study. The 196 patients analyzed in this study were divided into four groups: tocilizumab treatment as the first biologic group (TCZ first, 42 patients), tocilizumab as second/ third biologic group (TCZ second, 34 patients), etanercept as the first biologic group (ETN first, 103 patients) and etanercept as second/third group (ETN second, 17 patients). Visual analog scale (VAS), clinical disease activity index (CDAI), and modified health assessment questionnaire (mHAQ) scores at the initiation of biologic treatment and after 6 months of tocilizumab and etanercept therapy were measured and compared to clinical parameters and radiographical parameters among the four groups. CRP, MMP-3, VAS, CDAI, and HAQ were improved after 6 months of treatment in all groups. Improvement of clinical outcomes was correlated with CRP value, duration of RA, and Sharp scores at the initiation of treatment. Multivariate analysis demonstrated improvement in CDAI was significantly associated with the yearly progression of erosion according to the Sharp score in TCZ first group (OR, 1.5; 95% CI, 1.03–2.07) and was negatively associated with the duration of RA (OR, 0.49; 95% CI, 0.29–0.86) at the initiation of treatment with ETN first group. We identified the predictive factors for effective selection of tocilizumab and etanercept treatment and established the effectiveness of tocilizumab for the patients with rapid progressive joint erosion and etanercept for the early administration from diagnosis of RA.

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes hyperplasia of synovial tissue. Death receptor 3 (DR3) is a tumor necrosis factor receptor and binds to TL1A, a member of the TNF family. DR3 is involved in the mechanism of cell proliferation and apoptosis through NF-κB signaling. Suppression of DR3 in rheumatoid synovial fibroblasts (RA-FLS) is associated with hyperplasia of rheumatoid synovial tissue [1]. We previously revealed the expression profiles regulated by TL1A, suggesting that TL1A might affect the pathogenesis of RA, including proliferation, regulation of B cells and T cells, inflammation, and cytokine processing [2].Objectives:In this study, we investigated the gene expression profiles regulated by DR3 in RA-FLS to reveal how DR3 is involved in the pathogenesis of RA.Methods:RA-FLS were from patients with RA. Four individual lines of primary cultured RA-FLS were incubated either with 1000 ng/ml of human DR3-Fc protein or 1000ng/ml of human IgG1 as a control for 12h. Gene expressions were detected by microarray assay.Results:Microarray data analysis revealed that DR3 up-regulated or down-regulated the expression of various genes in RA-FLS (Figure). The function of regulated genes included protein-L-isoaspartate (D-aspartate) O-methyltransferase activity, carboxyl-O-methyltransferase activity, protein carboxyl O-methyltransferase activity, regulation of cilium assembly, O-methyltransferase activity, regulation of plasma membrane bounded cell projection assembly, regulation of cell projection assembly, regulation of organelle assembly, protein methyltransferase activity, and S-adenosylmethionine-dependent methyltransferase activity. The most up-regulated 2 genes by DR3 were KIAA1109 (KIAA1109), and adhesion G protein-coupled receptor A3 (ADGRA3). The most down-regulated 2 genes by DR3 were RNA exonuclease 2 (REXO2), and family with sequence similarity 120A (FAM120A).Conclusion:In this study, we first revealed the expression profiles of genes regulated by DR3 in RA-FLS. KIAA1109/TENR/IL2/IL21 gene is strongly associated with RA in European descent populations [3]. ADGRA3 is a member of G protein-coupled receptors (GPCRs). GPCRs associates with the regulation of cytoskeletal organization, the cell adhesion and migration, cell proliferation and apoptosis, and cell differentiation [4]. Loss of REXO2 affects cell growth and morphology [5], and REXO2 was identified as a target gene for inflammatory bowel disease-associated variants [6]. FAM120A regulates activity of Src kinase to protect cells from oxidative stress-induced apoptosis [7]. DR3 regulates the gene expressions of various key molecules in RA-FLS and may affect the pathogenesis of RA by regulating gene expression of RA-FLS.References:[1]Takami N. et al., Arthritis Rheuma. 2006;54:779-787.[2]Fukuda K. et al., Biomed Rep. 2019;1:1-5.[3]Teixeira VH. et al., Arthritis Research & Therapy. 2009;11:R45.[4]Hamann J. et al., Pharmacol Rev. 2015;67:338-367.[5]Bruni F, et al., PLoS One. 2013;8:e64670.[6]Hulur I, et al., BMC Genomics. 2015;16:138.[7]Tanaka M. et al., Mol Cell Biol. 2009;29:402-413.Disclosure of Interests:None declared

Background:Many blood vessels are generated in the hyperplastic synovial tissue of patients with rheumatoid arthritis (RA), and lead to chronic tissue inflammation and joint destruction [1]. Janus kinase (JAK) family consisting of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) are chain receptors which phosphorylate signal transducers and activators of transcription (STAT) and mediate inflammatory diseases including RA [2]. Nowadays, several JAK inhibitors such as Tofacitinib (TOF), Baricitinib (BAR) and Peficitinib (PEF) have been developed and demonstrated to have the inhibitory effects on inflammatory arthritis [3-5]. However, there were few reports concerning their effects on angiogenesis in vitro.Objectives:The purpose of the present study is to investigate the influence of JAK inhibitors on angiogenesis of human umbilical vein endothelial cell (HUVEC) activated by vascular endothelial growth factor (VEGF).Methods:The cell line of HUVECs were used for this study. The activity of proliferation and tube formation were analyzed by counting assay and tube formation assay, respectively.In counting assay, HUVECs (5 × 104cells/ml) were seeded onto 96-well cell culture plate with 20 ng/ml VEGF including various doses (0.1µM, 1µM, 5µM) of TOF, BAR or PEF. After 48 hours incubation at 37°C in a humidified atmosphere containing 5% CO2, cell proliferation of each groups was assessed using cell counting kit. In tube formation assay, HUVECs (5 × 104cells/ml) were treated with 20ng/ml VEGF including various dose (0.1µM, 1µM, 5µM) of TOF, BAR or PEF for 00 hours, then seeded onto 48-well plate applied with Matrigel. After 24 hours incubation on Matrigel, the capillary-like tube formation of each well was photographed using phase contrast microscopy. Tube formation were quantitated by measurement of the length of branch.Results:HUVECs were activated in proliferation and tube formation by VEGF treatment. And, the proliferation and tube formation of HUVECs activated by VEGF were suppressed by All of TOF, BAR and PEF. In particular, TOF and PEF could suppress them highly.Conclusion:This study showed the inhibitory effect of JAK inhibitors on proliferation and tube formation of HUVECs activated by VEGF. In particular, the angiogenesis of HUVECs activated by VEGF was highly suppressed by TOF and PEF. VEGF is reported to regulate the angiogenesis through multi JAK-STAT signaling pathways [6]. The inhibitory effects on angiogenesis of TOF, BAR and PEF might depend on the differences in their affinity for JAKs. VEGF has been shown to a have a central involvement in the angiogenic process in RA [7]. JAK inhibitors might suppress the angiogenesis in RA synovial tissues by inhibiting VEGF signaling.References:[1]Scott DL, et al. Rheumatoid arthritis. Lancet. 2010.[2]Banerjee S, et al. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017.[3]William D, et al. JAK inhibitors in dermatology: the promise of a new drug class. Journal of the American Academy of Dermatology. 2017.[4]Dhillon S. Tofacitinib: A Review in Rheumatoid Arthritis. Drugs. 2017.[5]Markham A, et al. Peficitinib: First Global Approval. Drugs. 2019.[6]Zhang HY, et al. Three important components in the regeneration of the cavernous nerve: brain-derived neurotrophic factor, vascular endothelial growth factor and the JAK/STAT signaling pathway. Asian journal of andrology. 2011.[7]Paleolog EM. Angiogenesis in rheumatoid arthritis. Arthritis research. 2002.Acknowledgments:noneDisclosure of Interests:None declared

Introduction: Analysis of predictive factors for the improvement of bone mineral density (BMD) in response to osteoporosis treatment is critical. Several studies reported on the analysis of bone turnover markers as a predictive factor for the improvement of BMD; however, few studies reported on predictive factors other than bone turnover markers. Thus, this study aimed to analyze other predictive factors for distal radial BMD improvement in response to denosumab treatment among patients with osteoporosis.Methods: We evaluated 133 patients with osteoporosis over a 24 month period. All patients received denosumab (60 mg) subcutaneously every 6 months. The BMD of the distal radius was assessed in all patients and serum concentrations of PINP and TRACP5b determined.Results: Denosumab treatment resulted in a 3.3% increase, from baseline, in distal radius BMD at 24 months. The average BMD change at 24 months was not significantly changed in relation to gender or prevalent medication. The average BMD change at 24 months was negatively correlated with patient’s age. Almost all the points of PINP and TRACP5b were not correlated with BMD except TRACP5b value at 24 months.Conclusions: We found that improvement of bone mineral density with denosumab treatment for osteoporosis is associated with young age of the patients. We recommend denosumab treatment for younger patients with osteoporosis.

Improving patient health-related quality of life (HRQOL) and prevention of bone fracture are important components of the treatment of osteoporosis. Our aim in this study was to evaluate the effect of denosumab treatment in improving HRQOL among patients with osteoporosis. Our analysis was based on 332 patients with osteoporosis, followed for 24 months. All patients received denosumab (60 mg) subcutaneously every 6 months. Bone mineral density (BMD) was assessed at the distal radius, with serum concentration of calcium, phosphate, P1NP, and TRACP5b also measured. HRQOL assessment included pain (visual analogue scale [VAS]) and the EQ-5D questionnaire. A multivariate analysis was performed to identify the possible confounders associated with deterioration in the EQ-5D utility score in response to denosumab treatment. Denosumab treatment yielded a 3.4% increase in BMD at 24 months. Serum levels of TRACP5b and P1NP decreased significantly, from baseline, at 6 months, with no effect on calcium and phosphate levels. Pain VAS and EQ-5D utility score improved significantly, from baseline, at 6 months, with the EQ-5D utility score correlating with the BMD at all time points of measurement over the 24-month period of observation. Knee osteoarthritis and multiple comorbidities were significantly associated with a worse HRQOL in response to denosumab treatment. Denosumab treatment increased BMD, with improvements in BMD correlating with improved HRQOL, supporting a possible benefit of using denosumab for the treatment of osteoporosis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Patients with rheumatoid arthritis (RA) are frequently complicated with gastric mucosal injury; however, there are few reports investigating gastroesophageal reflux disease (GERD) among patients with RA. We investigated the frequency of GERD and the correlation between GERD and the clinical characteristics of RA including patient's global assessment (PGA).Patients with RA were investigated for GERD using self-administered frequency scale for the symptoms of GERD (FSSG). The correlation between GERD and the clinical characteristics of RA was analyzed statistically.Two hundred and eleven patients in Japan were investigated. The prevalence of GERD among patients with RA (24.6%) was significantly higher than that in the Japanese population (11.5%) (p0.001). FSSG was positively correlated with modified health assessment questionnaire (mHAQ), PGA, evaluator's global assessment (EGA) (p0.001), disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) (p0.05), DAS28-C-reactive protein (CRP), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) (p0.001). The patients with GERD showed significantly higher scores in mHAQ, PGA, EGA, tenderness joint count, DAS28-ESR, DAS28-CRP, SDAI and CDAI (p0.001). Furthermore, the patients with GERD showed lower remission rates based on DAS28-ESR (p0.05), DAS28-CRP, SDAI and CDAI (p0.001).GERD complicated with RA increases PGA and the indices of disease activity. GERD symptoms analyzed using FSSG may be desirable to avoid the overestimation as part of the total management of patients with RA.

The selection of the correct entry point for stabilisation of long bone fractures and particularly of the humerus with intramedullary nailing is of paramount importance. The insertion of a nail from the correct entry point ensures anatomical alignment of the head and the shaft fragment. However, particularly for the humerus, the literature addressing this issue is obscure. Twenty cadaveric humeri without soft tissue attachment were studied. Two groups were studied: Group A (straight nail) and Group B (angled nail). A fracture of the surgical neck of the humerus was simulated. Then intramedullary nail was inserted through the correct entry hole. Displacement at the fracture site and force to reduce the displacement were measured. The average horizontal displacement was 2.5 ± 2.2 mm in Group A and 1.9 ± 1.1 mm in Group B. The humeral shaft tended to displace medially. The force required to reduce the produced displacement was usually less than 15 N. Anatomical reduction could not be obtained in 3/20 humeri even after applying a force of over 35 N. Our results of an average displacement of 2 mm following nail insertion, supports the significance of the entry point as a cause of loss of reduction at the fracture site post nail insertion. In most cases, anatomical reduction can be corrected with relative small forces, whereas in the rest the correction of the displacement is not feasible even with the application of substantial forces.

Background Music Therapy is the clinical and evidence-based use of music interventions to accomplish individualized goals within a therapeutic relationship by a credentialed professional who has completed an approved music therapy program. Music therapy interventions can be designed to alleviate pain, manage stress, and promote physical rehabilitation in addition to express feelings, enhance memories, improve communication, and promote wellness. Recently music therapy is much further innovated in rehabilitation for such as dementia and parkinsonism, however, few reports have been made for arthritis including rheumatoid arthritis (RA). Objectives Since 2010, we have held music therapy activity annually in monthly patient education classes for patients with RA. In this study we surveyed the effects of music therapy for patients with RA. Methods Music therapy activity was conducted by a credentialed music therapist, a volunteer pianist, hospital staffs, and healthcare students. Six Japanese songs were sung with a piano accompaniment. Three of 6 were sung and simultaneously played with chime bars (a sort of hand bells) following colored notes by the participants. General health condition, pain, and state anxiety were surveyed by self-rating questionnaire including 10cm visual analog scale (VAS), face pain rating scale, and State Trait Anxiety Index (STAI). Results were statistically analyzed with Wilcoxon signed-rank test or Student9s t-test. Results Thirty patients with RA (28 females and 2 males) were participated the survey. Twenty were in 60s, 10 in 50s and 10 in 70s. Modified health assessment questionnaire (mHAQ) of the attendee was 0.55±0.62 (0-2.6). VAS was significantly improved from 2.8±2.9 to 2.4±2.7 (p Conclusions Music therapy using musical instruments improves pains and physical and psychological conditions of patients with RA. Disclosure of Interest None declared

Background Cyclin-dependent kinases (CDKs) are recognized as a regulator of cell cycle progression, and CDK activation is regulated by CDK inhibitors. Whereas, many study reported the interaction between inflammation and osteoarthritis. Recently, Marves reported that p21 deficiency mice was susceptible to LPS-induced inflammation. However, how p21 works responsible for persistent inflammation of joints that occurs with osteoarthritis is unknown. The aim of this study is to investigate the p21 function about progressions of osteoarthritis in vivo. Objectives P21 knockout mice (B6.129S6 (Cg)-Cdkn1atm1Led/J) and C57Bl6/J (Wild type) mice were obtained from The Jackson Laboratory (Bar Harbor, Maine). Respectively 84 male mice at 10 week-old were used in this experiment. Methods Destabilization of the medial meniscus (DMM) was induced in the right knee and the sham group in the left knee. We sacrificed mice at 7 time points, non-operative group (control), postoperative 1day, 3day, 1week, 2weeks, 4weeks, and 8weeks. Each group contained 6 male mice. We collected blood samples and evaluate IL-1β expression by IL-1β ELISA Kit (ab100704: abcam). Post operated 1week and 8weeks, we sacrificed mice and scanned knee joint using μCT and watched changing of bone structure. Coronal histological sections were stained with H-E, Safranin O, and expression of F4/80, PCNA, IL-1β was analyzed by immunohistochemistry. Results ELISA: Serum levels of IL-1β were significantly elevated in p21 (-/-) mice at each time points except control group (Fig. 1). P21 (-/-) mice showed long lasting elevation of IL-1β compared with WT after DMM surgery. After postoperative 1w, IL-1β begin to increase slowly until postoperative 8weeks. Histrogical evaluation: We evaluated synovitis with H-E stain section. At postoperative 1 week, both p21 (-/-) and WT showed synovial membrane outgrowth. At 8week, synovitis settled and volume of synovial membrane decreased in WT. However, synovial inflammation was still occurred in p21 (-/-) mice (Fig. 2). F4/80 and PCNA immunohistochemistry showed surface linier of synovial membranes were strongly stained in p21 (-/-) mice compared with WT (Fig. 3, 4). Safranin O staining in joint cartilage tissues were evaluated by OARSI histopathology classification. P21 (-/-) mice post DMM surgery at 8 weeks model showed grade 6 in medial tibial plateau, grade 5 in medial femoral condyle. WT mice showed grade 0.5 in medial tibial plateau, grade 3 in medial femoral condyle (Fig. 5). These suggested that p21 deficiency was susceptible to osteoarthritis. μCT analysis: At control group there is no difference between p21 (-/-) and WT mice about their appearance (Fig. 6a). P21 (-/-) showed subchondral bone sclerotic change and generated multiple mineralized tissue compared with WT at 8 weeks post-surgery (Fig. 6b). Conclusions We demonstrated that the p21 deficiency was susceptible to osteoarthritis change in DMM models with systemic IL-1β expression, synovial macrophage infiltration (F4/80), and synovial cell proliferation (PCNA). Therefore, we conclude that p21 deficiency accelerates osteoarthritis with inflammation. References Mavers M, Cuda CM, et al. Cyclin-dependent kinase inhibitor p21, via its C-terminal domain, is essential for resolution of murine inflammatory arthritis. Arthritis and rheumatism. 2012;64(1):141-52. Disclosure of Interest None declared

Background Decoy receptor 3 (DcR3) is a secreted decoy tumor necrosis factor receptor (TNFR) and competitively binds and inhibits the TNF family including Fas-ligand (FasL), LIGHT, and TL1A. DcR3 is overexpressed in tumor cells and might benefit tumors by helping them to avoid cytotoxic and regulatory effects of the ligands. We previously reported that DcR3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated by TNF-alpha protects the cells from Fas-induced apoptosis [1]. Meanwhile, recent studies suggested that DcR3 directly induces osteoclast formation from monocytes, and that DcR3 triggers enhanced adhesion of monocytes via reverse signaling. We recently reported that DcR3 induces VLA-4 expression in THP-1 macrophages to inhibit cycloheximide-induced apoptosis [2], and that DcR3 binds to TL1A expressed on RA-FLS resulting in the negative regulation of cell proliferation induced by inflammatory cytokines [3]. Further, we newly reported the microarray data analysis revealed DcR3 regulates gene expression in RA-FLS. The profiles indicated shared interleukin (IL)-12B p40 subunit of IL-12 and IL-23 was up-regulated by DcR3 (fold change 1.65) [4]. Objectives In this study, we analysed IL-12B expression in RA-FLS stimulated with DcR3 in detail. Methods Real-time polymerase chain reaction (real-time PCR). RA and osteoarthritis (OA) -FLS were stimulated with various concentration of DcR3-Fc or control IgG1 for 12 hours. Further, RA-FLS were incubated with DcR3-Fc for 12 hours after overnight pre-incubation with anti-TL1A antibody. The relative expression levels of IL-12B mRNA were quantified by real-time PCR. Western blotting. RA-FLS was stimulated with 1000 ng/ml DcR3-Fc or control IgG1 for 24 hours. The expression of IL-12B p40 protein in RA-FLS was investigated by western blotting. Results Real-time PCR. Real-time PCR revealed that DcR3-Fc significantly increased the expression of IL-12B mRNA in RA-FLS in a dose dependent manner (113% with 10ng/ml, 135% with 100ng/ml, and 218% with 1000ng/ml) compared with control IgG1. In contrast, DcR3-Fc did not increase IL-12B mRNA in OA-FLS. Anti-TL1A antibody inhibited the up-regulation of IL-12B expression in RA-FLS induced by DcR3-Fc. Western blotting. Western blotting confirmed that IL-12B p40 protein in RA-FLS was increased when stimulated with DcR3-Fc. Conclusions IL-12 consisted of IL-12A (p35) and IL-12B induces Th1 immune responses to be linked with autoimmune diseases including psoriasis and inflammatory bowel disease. Meanwhile, IL-23 consisted of IL-23A (p19) and IL-12B is involved in the inflammatory pathway and linked to multiple sclerosis and inflammatory bowel disease [5]. In this study, we revealed that DcR3 increased the expression of IL-12B in RA-FLS in a disease-specific fashion by binding to membrane-bound TL1A as a ligand. DcR3 may affect the pathogenesis of RA through IL-12B. References Hayashi S. et al., Arthritis and Rheum, 56,1067-1074,2007 Tateishi K. et al., Biochem Biophys Res Commun, 389,593-598,2009 Takahashi M. et al., Int J Mol Med, 28,423-427,2011 Fukuda K. et al., Int J Mol Med, 32,910-916,2013 Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3991