Or Osteoarthritis Research Articles

A single-centre RetrospeCtive sTudy Investigating patient-reported outcomeS of extended dressing wear time for incisional healing following orthopaedic surgery: the ARCTIS study.

Orthopaedic surgery is an effective intervention for treating the symptoms of degenerative joint disease or osteoarthritis (OA). Frequent wound dressing changes, unless clinically indicated, can disrupt the healing process and increase the occurrence of incision site contamination. Protection from contamination is critical for surgical incisions and, therefore, undisturbed wound healing (UWH) in surgical wound management is vital. This article describes a retrospective study reporting the clinical performance of a self-adherent, absorbent postoperative dressing, with a focus on dressing wear time. A single-centre, retrospective electronic medical record review of a convenience sample of adult patients treated with a dressing (Mepilex Border Post Op; Mölnlycke, Sweden) following elective hip or knee replacement was undertaken. Data relating to dressing wear time, rationale for dressing changes and patient-reported outcomes were extracted from a mobile health application moveUP Therapy (moveUP NV, Belgium). Health-related quality of life assessment was conducted using the EQ-5D-5L questionnaire and orthopaedic-specific quality of life (QoL) indicator tools. Of the 558 records reviewed, 151 respondents (27.1%) reported outcomes relating to dressing wear time and frequency of dressing change. The average wear time of the first dressing was 13.6 days (second dressing: 5.3 days). The proportion of patients who wore the first dressing for 1-7 days, 8-13 days and for ≥14 days was 17.2%, 13.2% and 69.5%, respectively. Data from the completed questionnaires revealed improvement in QoL over time. The results of this study are a good indicator of the suitability of the postoperative dressing for a 14-day wear time, in line with the principles of UWH.

Contribution of the Musculoskeletal Ultrasound in the Diagnosis of Seronegative Rheumatoid Arthritis.

This is a study to investigate the value of musculoskeletal ultrasound for the early diagnosis of seronegative rheumatoid arthritis (SNRA); and to study the relationship between anti-cyclic citrullinated peptide antibody (anti-CCP) and the occurrence of bone erosion in rheumatoid arthritis (RA) detected by ultrasound. A total of 101 patients with RA or osteoarthritis (OA) admitted to the First Affiliated Hospital of Anhui Medical University from July 2022 to December 2023 were selected and divided into the SNRA group, the SPRA group, and the OA group. The patients' metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, and wrist joints of both hands were ultrasonically examined separately, and the extensor tendon, flexor tendon, synovium, joint surface, joint cavity, and bone surface were observed. The differences in the detection of joint effusion, bone erosion, and joint space narrowing were not statistically significant between SNRA group and OA group (P > .05), the differences in the detection of synovitis and tenosynovitis were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and OA group were significantly different (P < .05). The differences in synovitis, tenosynovitis, joint effusion, and joint space narrowing were not statistically significant between SNRA and SPRA groups (P > .05), and the differences in bone erosion were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and SPRA group were significantly different (P < .05). Logistic regression analysis showed that anti-CCP antibody was an influential factor for bone erosion in RA patients (P < .05). The ROC curve was plotted, and the optimal cut-off value of anti-CCP antibody was 356.5U/mL, at which time the AUC was 0.716, the sensitivity of diagnosing bone erosion was 0.714, the specificity was 0.694, and the Yoden index was 0.408. In summary, ultrasound is helpful for the early diagnosis of SNRA by evaluating the condition of joints, synovium, and tendon sheath, and when anti-CCP antibodies are positive, ultrasound is more likely to detect bone erosion. Ultrasound examination combined with anti-CCP antibody can further observe the joint lesions.

Dysregulated NUB1 and Neddylation Enhances Rheumatoid Arthritis Fibroblast-Like Synoviocyte Inflammatory Responses.

Fibroblast-like synoviocytes (FLS) contribute to the pathogenesis of rheumatoid arthritis (RA), in part due to activation of the proinflammatory transcription factor NF-κB. Neddylation is modulated by the negative regulator of ubiquitin-like protein (NUB) 1. We determined whether NUB1 and neddylation are aberrant in the models with RA FLS, thereby contributing to their aggressive phenotype. Models with RA or osteoarthritis (OA) FLS were obtained from arthroplasty synovia. Real-time quantitative polymerase chain reaction and Western blot analysis assessed gene and protein expression, respectively. NUB1 was overexpressed using an expression vector. NF-κB activation was assessed by stimulating FLS with interleukin (IL)-1β. Neddylation inhibitor (MLN4924) and proteasome inhibitor were used in migration and gene expression assays. MLN4924 was used in the model with K/BxN serum-transfer arthritis. Enhanced H3K27ac and H3K27me3 peaks were observed in the NUB1 promoter in the OA FLS compared with the RA FLS. NUB1 was constitutively expressed by FLS, but induction by IL-1β was significantly greater in the OA FLS. The ratio of neddylated cullin (CUL) 1 to nonneddylated CUL1 was lower in the OA FLS than the RA FLS. NUB1 overexpression decreased NF-κB nuclear translocation and IL-6 messenger RNA (mRNA) in IL-1β-stimulated the RA FLS. MLN4924 decreased CUL1 neddylation, NF-κB nuclear translocation, and IL-6 mRNA in IL-1β-stimulated the RA FLS. MLN4924 significantly decreased arthritis severity in the model with K/BxN serum-transfer arthritis. CUL1 neddylation and NUB1 induction is dysregulated in the models with RA, which increases FLS activation. Inhibition of neddylation is an effective therapy in an animal model of arthritis. These data suggest that the neddylation system contributes to the pathogenesis of RA and that regulation of neddylation could be a novel therapeutic approach.

Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts

Histone lysine methylation is thought to play a role in the pathogenesis of rheumatoid arthritis (RA). We previously reported aberrant expression of the gene encoding mixed-lineage leukemia 1 (MLL1), which catalyzes methylation of histone H3 lysine 4 (H3K4), in RA synovial fibroblasts (SFs). The aim of this study was to elucidate the involvement of MLL1 in the activated phenotype of RASFs. SFs were isolated from synovial tissues obtained from patients with RA or osteoarthritis (OA) during total knee joint replacement. MLL1 mRNA and protein levels were determined after stimulation with tumor necrosis factor α (TNFα). We also examined changes in trimethylation of H3K4 (H3K4me3) levels in the promoters of RA-associated genes (matrix-degrading enzymes, cytokines, and chemokines) and the mRNA levels upon small interfering RNA-mediated depletion of MLL1 in RASFs. We then determined the levels of H3K4me3 and mRNAs following treatment with the WD repeat domain 5 (WDR5)/MLL1 inhibitor MM-102. H3K4me3 levels in the gene promoters were also compared between RASFs and OASFs. After TNFα stimulation, MLL1 mRNA and protein levels were higher in RASFs than OASFs. Silencing of MLL1 significantly reduced H3K4me3 levels in the promoters of several cytokine (interleukin-6 [IL-6], IL-15) and chemokine (C–C motif chemokine ligand 2 [CCL2], CCL5, C-X-C motif chemokine ligand 9 [CXCL9], CXCL10, CXCL11, and C-X3-C motif chemokine ligand 1 [CX3CL1]) genes in RASFs. Correspondingly, the mRNA levels of these genes were significantly decreased. MM-102 significantly reduced the promoter H3K4me3 and mRNA levels of the CCL5, CXCL9, CXCL10, and CXCL11 genes in RASFs. In addition, H3K4me3 levels in the promoters of the IL-6, IL-15, CCL2, CCL5, CXCL9, CXCL10, CXCL11, and CX3CL1 genes were significantly higher in RASFs than OASFs. Our findings suggest that MLL1 regulates the expression of particular cytokines and chemokines in RASFs and is associated with the pathogenesis of RA. These results could lead to new therapies for RA.

How the Plants for Joints multidisciplinary lifestyle intervention achieved its effects: a mixed methods process evaluation

BackgroundPlants for Joints (PFJ) is a multidisciplinary intervention centered around a whole-food plant-based diet, physical activity, and sleep and stress management. The PFJ intervention successfully improved disease activity and symptoms in people with rheumatoid arthritis (RA) or osteoarthritis (OA), respectively, and metabolic health. To investigate how these effects were achieved a mixed methods process evaluation was conducted to understand the context, implementation, and mechanism of impact of the PFJ intervention. Also, the relationship between degree of implementation and lifestyle changes was explored.MethodsQuantitative and qualitative data were collected across the evaluation domains context (i.e. reach), implementation (i.e. recruitment and delivery), and mechanism of impact (i.e. responsiveness) of both the participants and coaches (incl. dietitians, sport coaches) according to the UK MRC guidelines for process evaluations. Data was collected from the participants via focus groups and questionnaires after the intervention, and interviews with coaches. Qualitative data were analyzed thematically, and quantitative data were assessed with descriptive statistics and linear regression analyses. Degree of implementation was quantified using a theory-driven implementation index score composed of different process evaluation constructs.ResultsOf the 155 participants who participated in the PFJ intervention, 106 (68%) took part in the questionnaire and 34 (22%) attended a focus group. Participants felt the intervention was complete, coherent, and would recommend the intervention to others (mean score 9.2 (SD 1.4) out of 10). Participants felt heard and empowered to take control of their lifestyle and health outcomes. Components perceived as most useful were self-monitoring, social support, practical and theoretical information, and (individual) guidance by the multidisciplinary team. Participants perceived the intervention as feasible, and many indicated it effectively improved their health outcomes. In an explorative analysis there was no significant difference in healthy lifestyle changes across implementation index score groups.ConclusionThis process evaluation offers important insights into why the PFJ intervention works and how the intervention can be optimized for future implementation. Results indicating the intervention’s high satisfaction, feasibility, and perceived effectiveness, further support the use of plant-based lifestyle interventions as an additional treatment option for patients with RA, OA, or other chronic diseases.Trial registrationInternational Clinical Trial Registry Platform numbers: NL7800, NL7801, and NL7802, all registered 17-06-2019.

Efficacy analysis of clinical serological indicators in the diagnosis of postoperative periprosthetic joint infection in patients with rheumatoid arthritis or osteoarthritis.

To investigate the incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) after primary joint arthroplasty; to analyze the optimal cut-off values of clinical serum markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer for the diagnosis of PJI in RA patients; and to explore their diagnostic efficacy and clinical significance. Clinical data of 15,702 patients with RA (578) or OA (15,124) who underwent total joint arthroplasty from 2013 to 2021 were retrospectively analyzed. Serum CRP, ESR, and D-dimer were recorded for each patient, and subject characteristic curves were used to determine the optimal threshold values of CRP, ESR, and D-dimer for RA-PJI and OA-PJI and to compare the areas under the curves to assess the diagnostic efficacy of the optimal threshold values of serologic indices for RA-PJI. The fiveyear incidence of PJI was 6.92% in RA patients and 0.67% in OA patients. The optimal thresholds of CRP, ESR, and D-dimer for the diagnosis of RA-PJI were respectively 13.85mg/L, 33.02mm/h, and 796.50ng/mL. The sensitivities of the optimal thresholds were respectively 67.6%, 62.2%, and 56.8%, and the specificities were 74.7%, 60.4%, and 74.4%. RA patients have a higher incidence of PJI than OA patients. The optimal thresholds for CRP, ESR, and d-dimer for the diagnosis of PJI were higher in RA patients than in OA patients, but the sensitivity and specificity of the diagnosis were not as good as in OA patients.

A review on osteoarthritis

Degenerative joint disease, or osteoarthritis (OA), is a prevalent chronic synovial joint condition characterized by non-inflammatory degeneration, leading to pain and restricted joint movement. OA patients navigate a spectrum of therapeutic options, from social media advice to prescriptions from primary care physicians. This article critically assesses evidence-based treatments for generalized or monoarticular OA, advocating multidisciplinary and multimodal therapy. Evaluation covers patient education, pharmaceuticals, complementary and alternative medicine, surgery, manual techniques, acupuncture, bracing, assistive devices, physical therapy, modalities, and interventional procedures (corticosteroid injection, viscosupplementation, pulsed radiofrequency). Optimal benefits emerge from early diagnosis and prevention combined with multidisciplinary and multimodal treatments. The review highlights the synergy of complementary therapies. Healthcare professionals should be well-versed in diverse OA management resources, emphasizing tailored treatment plans aligned with individual needs and encouraging healthier lifestyle choices for optimal patient outcomes.Top of Form

Diagnosis of periprosthetic joint infections in patients who have rheumatoid arthritis.

To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI.

Pharmacokinetics of a single oral dose of grapiprant in juvenile pigs (Sus scrofa domestica).

Both pet and research pigs can suffer from some degree of pain from surgery, injuries, or osteoarthritis (OA). Despite this, there is a paucity of data on safe and effective analgesia agents in pigs. Grapiprant is an EP4 antagonist that blocks the action of the pro-inflammatory prostanoid, PGE2 . It has shown efficacy in attenuating pain associated with ovariohysterectomy and OA in dogs. However, there are no data regarding grapiprant in pigs. Therefore, the pharmacokinetic profile of orally administered grapiprant to juvenile pigs (Sus scrofa domestica) was evaluated in this study. Seven juvenile pigs received 12 mg/kg grapiprant orally. Blood was collected from an indwelling jugular catheter using the push-pull method at set timepoints up to 48 hours. Sample analysis was performed with high-performance liquid chromatography. Mean grapiprant plasma concentration was 164.3 ± 104.7 ng/mL which occurred at 0.8 ± 0.3 h. This study demonstrated that grapiprant concentrations consistent with analgesia in dogs were reached at this dosage in pigs. Further studies are needed to evaluate the efficacy of grapiprant in pigs.

Iron regulates chondrocyte phenotype in haemophilic cartilage through the PTEN/PI3 K/AKT/FOXO1 pathway

ABSTRACTObjectiveOur previous study demonstrated that iron overload could lead to haemophilic cartilage destruction by changing chondrocyte phenotype. This change was caused by iron’s effect on chondrocyte expression of FGF23 and SOX9, in addition to iron-induced chondrocyte apoptosis and cartilage extracellular matrix degradation. However, the underlying mechanisms remain unclear. This study aimed to determine the mechanism by which iron influences chondrocyte phenotype in the pathogenesis of haemophilic cartilage destruction.MethodsThe expression of the PTEN/PI3K/AKT/FOXO1 signal pathway in the articular cartilage of patients with haemophilic arthritis (HA) or osteoarthritis (OA) was determined using western blot (WB). Additionally, we quantified the expression of iron-induced PTEN, PI3K, p-PI3K, AKT, p-AKT, FOXO1, and p-FOXO1 in primary human normal chondrocyte cells (HUM-iCell-s018) using WB.ResultsWe found that compared to that in patients with OA, the expression of PTEN, PI3K, AKT, and FOXO1 in the articular cartilage of patients with HA was up-regulated, while the expression of p-PI3K, p-AKT, and p-FOXO1 was down-regulated. Additionally, iron increased the expression of PTEN, PI3K, AKT, and FOXO1 and suppressed that of p-PI3K, p-AKT, and p-FOXO1 in chondrocytes in a dose-dependent manner.ConclusionsOur findings demonstrated that iron was involved in the pathogenesis of haemophilic cartilage destruction by affecting chondrocyte phenotype through the inhibition of the PTEN/PI3K/AKT/FOXO1 pathway.

Sox, Fox, and Lmx1b binding sites differentially regulate a Gdf5-Associated regulatory region during elbow development.

Introduction: The articulating ends of limb bones have precise morphology and asymmetry that ensures proper joint function. Growth differentiation factor 5 (Gdf5) is a secreted morphogen involved in cartilage and bone development that contributes to the architecture of developing joints. Dysregulation of Gdf5 results in joint dysmorphogenesis often leading to progressive joint degeneration or osteoarthritis (OA). The transcription factors and cis-regulatory modules (CRMs) that regulate Gdf5 expression are not well characterized. We previously identified a Gdf5-associated regulatory region (GARR) that contains predicted binding sites for Lmx1b, Osr2, Fox, and the Sox transcription factors. These transcription factors are recognized factors involved in joint morphogenesis and skeletal development. Methods: We used in situ hybridization to Gdf5, Col2A1, and the transcription factors of interest in developing chicken limbs to determine potential overlap in expression. We further analyzed scRNA-seq data derived from limbs and knees in published mouse and chicken datasets, identifying cells with coexpression of Gdf5 and the transcription factors of interest. We also performed site-directed mutatgenesis of the predicted transcription factor binding sites in a GARR-reporter construct and determined any change in activity using targeted regional electroporation (TREP) in micromass and embryonic chicken wing bioassays. Results: Gdf5 expression overlapped the expression of these transcription factors during joint development both by in situ hybridization (ISH) and scRNA-seq analyses. Within the GARR CRM, mutation of two binding sites common to Fox and Sox transcripstion factors reduced enhancer activity to background levels in micromass cultures and in ovo embryonic chicken wing bioassays, whereas mutation of two Sox-only binding sites caused a significant increase in activity. These results indicate that the Fox/Sox binding sites are required for activity, while the Sox-only sites are involved in repression of activity. Mutation of Lmx1b binding sites in GARR caused an overall reduction in enhancer activity in vitro and a dorsal reduction in ovo. Despite a recognized role for Osr2 in joint development, disruption of the predicted Osr2 site did not alter GARR activity. Conclusion: Taken together, our data indicates that GARR integrates positive, repressive, and asymmetrical inputs to fine-tune the expression of Gdf5 during elbow joint development.

Opiate Antagonists for Chronic Pain: A Review on the Benefits of Low-Dose Naltrexone in Arthritis versus Non-Arthritic Diseases.

Chronic pain conditions create major financial and emotional burdens that can be devastating for individuals and society. One primary source of pain is arthritis, a common inflammatory disease of the joints that causes persistent pain in affected people. The main objective of pharmacological treatments for either rheumatoid arthritis (RA) or osteoarthritis (OA) is to reduce pain. Non-steroidal anti-inflammatory drugs, opioids, and opioid antagonists have each been considered in the management of chronic pain in arthritis patients. Naltrexone is an oral-activated opioid antagonist with biphasic dose-dependent pharmacodynamic effects. The molecule acts as a competitive inhibitor of opioid receptors at high doses. However, naltrexone at low doses has been shown to have hormetic effects and provides relief for chronic pain conditions such as fibromyalgia, multiple sclerosis (MS), and inflammatory bowel disorders. Current knowledge of naltrexone suggests that low-dose treatments may be effective in the treatment of pain perception in chronic inflammatory conditions observed in patients with either RA or OA. In this review, we evaluated the therapeutic benefits of low-dose naltrexone (LDN) on arthritis-related pain conditions.

Productivity Loss Across Socioeconomic Groups Among Patients With Low Back Pain or Osteoarthritis: Estimates Using the Friction-Cost Approach in Norway.

Our aim was to estimate the productivity loss (PL) among patients with low back pain (LBP) or osteoarthritis (OA) across socioeconomic groups, using the friction-cost approach (FCA). A total of 175,550 patients aged 18-65 years were included at their first diagnosis in specialty care between 2011 and 2016. PL was calculated for the year following diagnosis using individual wages, while adjusting for the friction length at 78 days per episode, a team production multiplier at 1.6, compensation mechanisms of 26.8%, and a chain-of-vacancies multiplier at 3.95. We included a simpler FCA model, omitting the latter three parameters, and a human capital approach (HCA) model. Socioeconomic stratifications were created based on education and income. One-way sensitivity analysis was used to assess the influence of the parameters in the full FCA model. The overall mean number of absent days was 23, while it was 25.3 and 20.1 for those with low and high education levels. The per-patient friction costs were €4395 among all patients and when extending the friction length to 98 days costs were €4342. For those with low and high education levels, the costs were €3671 and €4464, respectively. The costs in the simple FCA and HCA models were €1539 and €2088. Socioeconomic status and model design are sources of variation in PL. In health economic applications with PL and in patient populations with large socioeconomic differences, adjusting for these factors may be as important as sensitivities in parameters such as the friction length.

Evaluation of 18F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis.

Fibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[18F] F-NOTA-labeled FAP inhibitor 04(18F-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis. Fibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between 18F-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated. Collagen-induce arthritis (CIA) mice models were established and treated with methotrexate (MTX) or etanercept (ETC). Then, PET imaging was performed 24h following 18F-FAPI-04 injection. The imaging results were compared by assessing macroscopic arthritis scores and histological staining. 18F-FAPI-04 uptake was obvious in RA FLSs that characterizing FAP activation. The higher the uptake of 18F-FAPI-04, the more severity of the inflammatory phenotype in RA FLS. Furthermore, the uptake of 18F-FAPI-04 in inflamed joints could be found even before the deformity of the parental joints could be observed by histological examination. Both MTX and ETC were effective in inhibiting the progression of arthritis in CIA mice was confirmed by macroscopic, histological, and radiographic pathology scores. Importantly, 18F-FAPI-04 uptake declined accordingly in CIA models following MTX and ETC treatment. These findings suggest that PET imaging of 18F-FAPI-04 can be used to monitor treatment response in RA, and is more sensitive in disease speculation than macroscopic arthritis scoring.

MYC promotes fibroblast osteogenesis by regulating ALP and BMP2 to participate in ectopic ossification of ankylosing spondylitis

BackgroundEctopic ossification is an important cause of disability in patients with ankylosing spondylitis (AS). Whether fibroblasts can transdifferentiate into osteoblasts and contribute to ossification remains unknown. This study aims to investigate the role of stem cell transcription factors (POU5F1, SOX2, KLF4, MYC, etc.) of fibroblasts in ectopic ossification in patients with AS.MethodsPrimary fibroblasts were isolated from the ligaments of patients with AS or osteoarthritis (OA). In an in vitro study, primary fibroblasts were cultured in osteogenic differentiation medium (ODM) to induce ossification. The level of mineralization was assessed by mineralization assay. The mRNA and protein levels of stem cell transcription factors were measured by real-time quantitative PCR (q-PCR) and western blotting. MYC was knocked down by infecting primary fibroblasts with lentivirus. The interactions between stem cell transcription factors and osteogenic genes were analysed by chromatin immunoprecipitation (ChIP). Recombinant human cytokines were added to the osteogenic model in vitro to evaluate their role in ossification.ResultsWe found that MYC was elevated significantly in the process of inducing primary fibroblasts to differentiate into osteoblasts. In addition, the level of MYC was remarkably higher in AS ligaments than in OA ligaments. When MYC was knocked down, the expression of the osteogenic genes alkaline phosphatase (ALP) and bone morphogenic protein 2 (BMP2) was decreased, and the level of mineralization was reduced significantly. In addition, the ALP and BMP2 were confirmed to be the direct target genes of MYC. Furthermore, interferon-γ (IFN-γ), which showed high expression in AS ligaments, was found to promote the expression of MYC in fibroblasts in the process of ossification in vitro.ConclusionsThis study demonstrates the role of MYC in ectopic ossification. MYC may act as the critical bridge that links inflammation with ossification in AS, thus providing new insights into the molecular mechanisms of ectopic ossification in AS.

More complications and higher transfusion rate in patients with rheumatoid arthritis than osteoarthritis undergoing total hip arthroplasty.

Total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) has been associated with an increased risk of periprosthetic joint infection, periprosthetic fractures, dislocations, and post-operative blood transfusion. However, higher post-operative blood transfusion is unclear whether it reflects peri-operative blood loss or is characteristic of RA. This study aimed to compare the complications, allogenic blood transfusion, albumin use, and peri-operative blood loss between patients who underwent THA because of RA or osteoarthritis (OA). Patients undergoing cementless THA for hip RA (n = 220) or hip OA (n = 261) at our hospital between 2011 and 2021 were retrospectively enrolled. Deep vein thrombosis, pulmonary embolism, myocardial infarction, calf muscular venous thrombosis, wound complications, deep prosthetic infection, hip prosthesis dislocation, periprosthetic fractures, 30-day mortality, 90-day readmission, allogeneic blood transfusion, and albumin infusions were considered as primary outcomes, while secondary outcomes included the number of perioperative anaemia patients as well as total, intra-operative, and hidden blood loss. Compared to the OA group, patients with hip RA showed significantly higher rates of wound aseptic complications, hip prosthesis dislocation, homologous transfusion, and albumin use. RA patients also showed a significantly higher prevalence of pre-operative anemia. However, no significant differences were observed between the two groups in total, intra-operative, or hidden blood loss. Our study suggests that RA patients undergoing THA are at a higher risk of wound aseptic complications and hip prosthesis dislocation than patients with hip OA. Pre-operative anaemia and hypoalbuminaemia in patients with hip RA place them at a significantly higher risk of post-operative blood transfusion and use of albumin.

Magnetically Guided Intracartilaginous Delivery of Kartogenin Improves Stem Cell-Targeted Degenerative Arthritis Therapy.

Degenerative joint disease or osteoarthritis (OA) is a leading cause of disability worldwide. Intra-articular injection is the mainstay nonsurgical treatment for OA. However, dense cartilage and a lack of vasculature often limit the ability of drugs to reach cell or tissue targets at the concentrations necessary to elicit the desired biological response. Kartogenin (KGN), a small molecular compound, possesses a strong capacity to promote chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the rapid clearanceof KGN from the intra-articular cavitylimits its feasibility. We constructed a magnetically guided biodegradable nanocarrier system (MNP) which enabled intracartilaginous delivery of KGN to promote chondrogenic differentiation by MSCs embedded within the articular matrix. Moreover, in preclinical models of OA, KGN-loaded MNPs exhibited increased tissue penetration and retention within the joint matrix under external magnetic guidance. Histological examination showed that compared with KGN alone, KGN-loaded MNPs enhanced chondrogenic differentiation and improved the structural integrity of both articular cartilage and subchondral bone. This study demonstrates a practical method for intracartilaginous delivery using engineered nanocarriers, thus providing a new strategy to improve the efficacy of molecular therapeutic agents in the treatment of OA.

Mechanical stress-caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1.

Sirtuin1 (Sirt1)/forkhead box O1 (FoxO1) axis has been reported as a crucial regulator involved in chondral homeostasis of healthy or osteoarthritis (OA) cartilage. In our study, the aim is to investigate whether dioscin functions as an activator of Sirt1/FoxO1 to protect against mechanical stress-induced chondrocyte dysfunction in vitro and in vivo models.HERB and PubChem databases were implemented to predict dioscin-related gene targets. Cell and mouse models of OA were established to determine the pharmacological value of dioscin, a steroidal saponin. Cartilage loss in the knee joint was detected by Safranin O staining. Phosphorylation and nucleocytoplasmic shuttling of FoxO1 was observed in mechanical stress-stimulated chondrocyte and anterior cruciate ligament transection-induced cartilage injury. However, dioscin treatment repressed FoxO1 phosphorylation and cytoplasmic transfer and elevated Sirt1 protein expression. Dioscin treatment reversed mechanical stress-induced growth inhibition and apoptosis of chondrocytes and improved cartilage degradation and bone loss in the epiphysis of the distal femur. Moreover, dioscin could maintain the normal phenotype of chondrocytes via mediating multiple gene expressions. Dioscin inhibited apoptosis and metabolic disorders in OA-like chondrocytes via maintaining the transcriptional activity of FoxO1 and enhancing Sirt1 expression. Dioscin might be a potential Sirt1 activator providing a novel therapeutic schedule for the treatment of OA.

A non‐randomised pragmatic trial for the early detection and prevention of surgical wound complications using an advanced hydropolymer wound dressing and smartphone technology: The EDISON trial protocol

Total hip or knee arthroplasty is a highly effective intervention for treating the symptoms of degenerative joint disease or osteoarthritis (OA), often an unwelcome consequence of obesity. A safe and common surgical procedure, hip and knee arthroplasty procedures are not immune to the occurrence of postoperative complications such as surgical site infection (SSI) or surgical wound dehiscence (SWD). While published rates of SSI following hip or knee arthroplasty are low, 1% to 2% in some cases, it is the resulting wound complication and its clinical management and the impact on patient well-being and return to daily life for the 1% to 2% that is of concern. Postoperative complications such as SSI are a major cost driver to the health care system following arthroplasty and often result in extended lengths of stay, readmission for further surgery, primary and community nursing visits, and are a costly burden to health care settings. Early identification of a wound complication through post-discharge surveillance using a fully transparent dressing and smartphone technology and patient education may ameliorate contributing factors or reduce the likelihood of a complication occurring in the first instance. This clinical trial is a non-randomised pragmatic convenience sample carried out in 200 participants of both sexes receiving either a TKA or THA. There will be equal allocation to two groups (100 hips and 100 knees), with 50 in each allocation receiving the interventional dressing and 50 as control. The dressing will be applied prior to discharge and participants will be provided with education on postoperative wound care, when to contact home care nursing for a potential wound problem, and use of their smartphone to capture and send images of their incision site to the study nurses. Participants will also be followed up by home care nursing services at day 14 for suture removal and wound assessment. Participants will complete a patient-reported outcomes survey on day 14 and followed up on day 30 after surgery for wound assessment. The results of this trial may provide a novel pathway using a fully transparent dressing and digital technologies for the prevention of acute readmissions because of wound complications through early detection and intervention.

Automated Detection of Knee Cartilage Region in X-ray Image

The prevalence of a symptomatic knee or osteoarthritis (OA) is approximately 9.6% in men and 18.0% in women over 60 years of age according to the OARSI 2016 report. Using early on-stage clinical qualitative assessments through means of X-ray scans, the cartilage health and degradation of an individual can be monitored through cartilage shape and surface over time. In this paper, we implement the application of transfer learning models such as InceptionV3, Xception and DenseNet201 for feature extraction of a rebalanced 1,000 knee X-ray images taken from Osteoarthritis Initiative (OAI) dataset with 5 classes graded 0–4 according to Kellgren-Lawrence grading split into a 70/15/15 training/validation/testing split. The features extracted are subsequently fed into machine learning classifiers, namely support vector machine (SVM). An average multiclass accuracy of 71.33% was achieved for hyperparameter fine-tuned DenseNet201-SVM model.