Progression Of Arthritis Research Articles

Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis.

Background/Objectives: 25-hydroxy vitamin D (25-OH-D) is a fat-soluble compound that plays many essential functions, including bone formation, neuromuscular functions, and prevention of osteoporosis and inflammation. Recent data indicate that its metabolites are associated with rheumatoid arthritis (RA) progression and neuropathic pain in RA patients. We aimed to assess the effect of RA pharmacotherapy and seasonal variation on serum levels of 25-OH-D in RA patients who received treatment with methotrexate (MTX) or leflunomide (LEF) for at least one year. Methods: This study is a retrospective analysis of data collected from 101 patients with RA who received treatment for at least one year. All of them have supplemented 25-OH-D (2000 IU daily) for at least one year. Results: We observed a significant seasonal variation in 25-OH-D concentration (p = 0.004). Moreover, there were significant differences (p = 0.03) between LEF (50.63 ± 17.73 ng/mL) and MTX (34.73 ± 14.04 ng/mL) treatment groups, but only for the summer population. A correlation was observed between 25-OH-D and RA duration-once again, in the summer population (the whole group-r = -0.64; treatment subgroups-r = -0.82 for LEF and -0.61 for MTX). Deficiency of 25-OH-D (below 20 ng/mL) was confirmed in 28.7% of patients, while 18.8% had suboptimal 25-OH-D levels (20-30 ng/mL). Conclusions: Our results showed that both RA pharmacotherapy and seasonal variation affect the serum levels of 25-OH-D in patients with active RA.

Fcgr2b and Fcgr3 are the major genetic factors for cartilage antibody-induced arthritis, overriding the effect of Hc encoding complement C5.

Like rheumatoid arthritis (RA) in humans, collagen-induced arthritis (CIA) in mice is associated with not only MHC class II genetic polymorphism but also, to some extent, with other loci including genes encoding Fc gamma receptors (FCGRs) and complement C5. In this study, we used a cartilage antibody-induced arthritis (CAIA) model in which arthritis develops within a 12-h timeframe, to determine the relative importance of FCGRs and C5 (Hc). In CAIA, inhibiting or deleting FCGR3 substantially hindered arthritis development, underscoring the crucial role of this receptor. Blocking FCGR3 also reduced the levels of FCGR4, and vice versa. When employing an IgG1 arthritogenic cocktail that exclusively interacts with FCGR2B and FCGR3, joint inflammation was promptly initiated in Fcgr2b--mice but not in Fcgr3--mice, suggesting that FCGR3 is sufficient for CAIA development. Regarding complement activation, Fcgr2b++.Hc** mice with C5 mutated were fully resistant to CAIA, whereas Fcgr2b--.Hc** mice developed arthritis rapidly. We conclude that FCGR3 is essential and sufficient for CAIA development, particularly when induced by IgG1 antibodies. The human ortholog of mouse FCGR3, FCGR2A, may be associated with RA pathogenesis. FCGR2B deficiency allows for rapid arthritis progression and overrides the resistance conferred by C5 deficiency.

Mid-Term Outcome of Superior Capsular Reconstruction Using Fascia Lata Autograft (At Least 6 mm in Thickness) Results in High Retear Rate and No Improvement in Muscle Strength

To report and evaluate clinical and radiologic outcomes of superior capsular reconstruction (SCR) using fascia lata autograft in patients with irreparable rotator cuff tears (IRCTs) over a mid-term duration and to assess the overall survival rate of the graft. We retrospectively reviewed patients who underwent SCR with fascia lata autograft between June 2017 and August 2018. The graft, folded 3 or 4 times, achieved a minimum thickness of 6 mm during the surgical procedure. The inclusion criteria encompassed patients with isolated supraspinatus IRCTs or posterosuperior IRCTs exhibiting poor muscle quality (Goutallier grade ≥3) and without arthritis (Hamada grade ≤ 2). The exclusion criteria included lack of follow-up data or magnetic resonance imaging. Clinical assessments included the visual analog scale score, Constant score, and American Shoulder and Elbow Surgeons (ASES) score; active range of motion; and strength. Radiographic analysis included the acromiohumeral distance, Hamada grade, and graft integrity at final follow-up. A Kaplan-Meier curve was generated to depict SCR graft survivorship. In total, 45 patients (mean age, 64.8 ± 5.7 years) were included, and the average follow-up duration was 63.2 ± 5.9 months (range, 50-79 months). There was significant improvement in pain (visual analog scale score of 4.4 ± 1.3 preoperatively vs 1.4 ± 0.4 at final follow-up, P < .001). Yet, 18 patients (40.0%) and 17 patients (37.7%) achieved the minimal clinically important difference in the ASES score and Constant score, respectively. Active forward elevation increased from 119° ± 23° to 137° ± 23° (P < .001), and external rotation at the side improved from 29° ± 11° to 36° ± 12° (P= .002). However, strength did not exhibit improvement in any direction. The acromiohumeral distance decreased from 8.5 ± 1.7 mm to 6.5 ± 1.9 mm (P < .001), and the Hamada grade increased from 1.1 ± 0.3 to 1.8 ± 1.1 (P < .001). Finally, the infection rate was 13.3% (n= 6). Despite a substantial graft retear rate of 62.2%, SCR led to a significant improvement in pain. Nonetheless, 18 patients (40.0%) and 17 patients (37.7%) achieved the minimal clinically important difference in the ASES score and Constant score, respectively. Forward elevation and external rotation at the side showed significant improvement, but no improvement in muscle strength was observed. Finally, significant arthritis progression was observed. Level IV, retrospective case series.

Corrections to "A Sub-Pixel Accurate Quantification of Joint Space Narrowing Progression in Rheumatoid Arthritis".

Presents corrections to the article "A Sub-Pixel Accurate Quantification of Joint Space Narrowing Progression in Rheumatoid Arthritis".

Joint-preserving treatment for global irreparable rotator cuff tears: combined anterior Latissimus dorsi and Teres major tendon transfer.

Treating global irreparable rotator cuff tears (GIRCTs) that involve both antero-and postero-superior cuff tendon tears could be a challenging problem. There has been limited joint-preserving treatment options in high-demand patients with minimal glenohumeral arthritis. The study aims to assess the clinical outcome of combined anterior latissimus dorsi and teres major tendon (aLDTM) transfer for patients with both GIRCTs and minimal glenohumeral arthritis. This retrospective study included patients who underwent combined aLDTM transfer for GIRCTs between 2018 May and 2020 October. Clinical outcomes include pain VAS, Constant, American Shoulder and Elbow Society (ASES), University of California Los Angeles (UCLA), activities of daily living requiring active internal rotation (ADLIR) score, active range of motion (aROM), strength, rates of pseudoparalysis or pseudoparesis reversal and return to work. Radiographic assessment included the acromiohumeral distance (AHD), Hamada grade, and transferred tendon integrity at final follow-up. 23 patients (mean age: 64.7 ± 5.9years [55-74]) were included and the mean follow-up period was 28.2 ± 4.3 [24‒36] months. Postoperatively, VAS, Constant, ASES, UCLA, and ADLIR scores significantly improved at final follow-up (P < .001). Postoperative aROM was significantly improved in forward elevation (FE) to 129° ± 29°, abduction (ABD) to 105° ± t3°, and internal rotation (IR) at back to 5.9 ± 2.5. Strength of both FE and IR were also significantly improved (P < .001). Patients with preoperative pseudoparalysis (2 of 4 patients) and pseudoparesis (6 of 6 patients) experienced a reversal. No significant change in AHD and hamada grade was confirmed at final follow-up. 3 patients experienced partial tear of the transferred tendon. In this study, we found significant improvement in clinical outcomes with no significant progression of arthritis by final follow-up. The aLDTM transfer could be an alternative choice of joint-preserving treatment option for young and active patients with GIRCTs and minimal glenohumeral arthritis. However, large and long-term studies should be conducted to establish its adequacy. Case series. IV.

Soluble CD147 regulates endostatin via its effects on the activities of MMP-9 and secreted proteasome 20S.

During progression of rheumatoid arthritis (RA), angiogenesis provides oxygen and nutrients for the cells' increased metabolic demands and number. To turn on angiogenesis, pro-angiogenic factors must outweigh anti-angiogenic factors. We have previously shown that CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) can induce the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) in a co-culture of the human HT1080 fibrosarcoma and U937 monocytic-like cell lines. However, whether CD147 influences anti-angiogenic factors was not known. We now show that relative to single cultures, the co-culture of these cells not only enhanced pro-angiogenic factors but also decreased the anti-angiogenic factors endostatin and thrombospondin-1 (Tsp-1), generally increasing the angiogenic potential as measured by a wound assay. Using anti-CD147 antibody, CD147 small interfering RNA (siRNA), and recombinant CD147, we demonstrate that CD147 hormetically regulates the generation of endostatin but has no effect on Tsp-1. Since endostatin is cleaved from collagen XVIII (Col18A), we applied different protease inhibitors and established that MMP-9 and proteasome 20S, but not cathepsins, are responsible for endostatin generation. MMP-9 and proteasome 20S collaborate to synergistically enhance endostatin generation, and in a non-cellular system, CD147 enhanced MMP-9 activity and hormetically regulated proteasome 20S activity. Serum samples obtained from RA patients and healthy controls mostly corroborated these findings, indicating clinical relevance. Cumulatively, these findings suggest that secreted CD147 mediates a possibly allosteric effect on MMP-9 and proteasome 20S activities and can serve as a switch that turns angiogenesis on or off, depending on its ambient concentrations in the microenvironment.

My orthopaedic surgeon suggests a unicompartmental knee replacement: a detailed look at the long-term outcomes of a single surgeon's practice.

This single surgeon case series with up to 29-year follow-up evaluated the survival of the Oxford unicompartmental knee replacement (UKR) for isolated medial compartment osteoarthritis. Four hundred and four knees in 330 patients were followed for between 12 days to 29 years, with an average of 13 years. Kaplan-Meier survival estimates were calculated using revision for total knee replacement and re-operation for any reason over 5-year intervals. Revision and reoperation rates per 100 component years were used to compare subsets, cemented and uncemented prostheses and Phase 2 and Phase 3 instrumentation. Of 404 UKRs, 292 (72%) were cemented, 96 (24%) uncemented and 16 hybrid (4%); 137 (34%) were undertaken using Phase 2 instrumentation and 267 (66%) Phase 3 instrumentation. Estimated revision-free implant survival at 20 years was 78%, and estimated reoperation-free survival at 20 years was 72%. Unicompartmental knee replacement is a very successful procedure, with 78% of knees remaining revision-free at 20 years. Progression of lateral compartment arthritis was the most common cause for revision, affecting 60% of revision cases. There was no significant difference in the revision or reoperation rate between cemented and uncemented prostheses or Phase 2 and minimally invasive Phase 3 instrumentation.

Lipid mediators obtained from docosahexaenoic acid by soybean lipoxygenase attenuate RANKL-induced osteoclast differentiation and rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by persistent inflammation and joint destruction. A lipid mediator (LM, namely, 17S-monohydroxy docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50) produced by soybean lipoxygenase from DHA, exhibits anti-inflammatory activity. In this study, we determined the effect of LM on collagen antibody-induced arthritis (CAIA) in mice and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in RAW264.7 cells. LM effectively downregulated the expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K, inhibited osteoclast formation, and suppressed the NF-κB signaling pathway in vitro. In vivo, LM at 10 μg/kg/day significantly decreased paw swelling and inhibited progression of arthritis in CAIA mice. Moreover, proinflammatory cytokine (tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-17, and interferon-γ) levels in serum were decreased, whereas IL-10 levels were increased following LM treatment. Furthermore, LM alleviated joint inflammation, cartilage erosion, and bone destruction in the ankles, which may be related to matrix metalloproteinase and Janus kinase (JAK)–signal transducer and activators of transcription (STAT) signaling pathway. Our findings suggest that LM attenuates arthritis severity, restores serum imbalances, and modifies joint damage. Thus, LM represents a promising therapy for relieving RA symptoms.

Intra-articular injection of stigmasterol-loaded nanoparticles reduce pain and inhibit the inflammation and joint destruction in osteoarthritis rat model: A pilot study.

Stigmasterol, a plant-derived sterol, sharing structural similarity with cholesterol, has demonstrated anti-osteoarthritis (OA) properties, attributed to its antioxidant and anti-inflammatory capabilities. Given that OA often arises in weight bearing or overused joints, prolonged localized treatment effectively targets inflammatory aspects of the disease. This research explored the impact of stigmasterol-loaded nanoparticles delivered via intra-articular injections in an OA rat model. Employing mesoporous silica nanomaterials (MSNs) combined with β-cyclodextrin (β-CD) as a vehicle, stigmasterol was loaded in conjunction with tannic acid, forming stigmasterol/β-CD-MSNs to facilitate a sustained stigmasterol release. The study employed RAW 264.7 cells to examine the in vitro cytotoxicity and anti-inflammatory effect of stigmasterol/β-CD-MSNs. For in vivo experimentation, we used healthy control rats and monosodium iodoacetate (MIA)-induced OA rats, separated into five groups, varying the injection substances. In vitro findings indicated that stigmasterol/β-CD-MSNs suppressed the mRNA expression of key pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-3 in a dose-dependent manner. In vivo experiments revealed a substantial decrease in the mRNA levels of pro-inflammatory factors in the stigmasterol(50µg)/β-CD-MSN group compared to the others. Macroscopic, radiographic, and histological evaluations established that intra-articular injections of stigmasterol/β-CD-MSNs inhibited cartilage degeneration and subchondral bone deterioration. Therefore, in a chemically induced OA rat model, intra-articular stigmasterol delivery was associated with reduction in both local and systemic inflammatory responses, alongside a slowdown in joint degradation and arthritic progression.

Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis

Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

PH and ROS Dual-Sensitive Nanocarriers for the Targeted Co-Delivery and On-Demand Sequential Release of Tofacitinib and Glucosamine for Synergistic Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) progression involves multiple cell types, and sequential drug action on target cells is necessary for RA treatment. Nanocarriers are widely used for RA treatment; however, the targeted delivery and on-demand release of multiple drugs remains challenging. Therefore, in this study, a dual-sensitive polymer is developed using chondroitin sulfate (CS) for the co-delivery of the cartilage repair agent, glucosamine (GlcN), and anti-inflammatory drug, tofacitinib (Tof). In the joint cavity, acidic pH facilitates the cleavage of GlcN from CS polymer to repair the cartilage damage. Subsequently, macrophage uptake via CS-CD44 binding and intracellular reactive oxygen species (ROS) mediate conversion of (methylsulfanyl)propylamine to a hydrophilic segment jointly triggered rapid Tof/GlcN release via micelle disassembly. The combined effects of Tof, GlcN, and ROS depletion promote the M1-to-M2 polarization shift to attenuate inflammation. The synergistic effects of these agents against RA are confirmed in vitro and in vivo. Overall, the dual pH/ROS-sensitive CS nanoplatform simultaneously delivers GlcN and Tof, providing a multifunctional approach for RA treatment with synergistic drug effects.

The gut homeostasis-immune system axis: novel insights into rheumatoid arthritis pathogenesis and treatment.

Rheumatoid arthritis is a widely prevalent autoimmune bone disease that imposes a significant burden on global healthcare systems due to its increasing incidence. In recent years, attention has focused on the interaction between gut homeostasis and the immune system, particularly in relation to bone health. Dysbiosis, which refers to an imbalance in the composition and function of the gut microbiota, has been shown to drive immune dysregulation through mechanisms such as the release of pro-inflammatory metabolites, increased gut permeability, and impaired regulatory T cell function. These factors collectively contribute to immune system imbalance, promoting the onset and progression of Rheumatoid arthritis. Dysbiosis induces both local and systemic inflammatory responses, activating key pro-inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-6, and Interleukin-17, which exacerbate joint inflammation and damage. Investigating the complex interactions between gut homeostasis and immune regulation in the context of Rheumatoid arthritis pathogenesis holds promise for identifying new therapeutic targets, revealing novel mechanisms of disease progression, and offering innovative strategies for clinical treatment.

IGF2BP3 regulates the expression of RRM2 and promotes the progression of rheumatoid arthritis via RRM2/Akt/MMP-9 pathway.

Rheumatoid arthritis (RA) is a common inflammatory and autoimmune disease. Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) is a crucial and a rate-limiting enzyme responsible for deoxynucleotide triphosphate(dNTP) production. We have found a high expression level of RRM2 in patients with RA, but the molecular mechanism of its action remains unclear. We analyzed the expression of hub genes in RA using GSE77298 datasets downloaded from Gene Expression Omnibus database. RRM2 and insulin-like growth factor-2 messenger ribonucleic acid (mRNA)-binding protein 3 (IGF2BP3) gene knockdown was achieved by infection with lentiviruses. The expression of RRM2, IGF2BP3, matrix metalloproteinase (MMP)-1, and MMP-9 were detected via western blotting assay. Cell viability was detected via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MeRIP-qRT-PCR was performed to test the interaction of IGF2BP3 and RRM2 mRNA via m6A modification. Cell proliferation was determined by clone formation assay. Migration and invasion assays were performed using transwell Boyden chamber. RRM2 and IGF2BP3 were highly expressed in clinical specimens and tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β-stimulated synovial cells. RRM2 and IGF2BP3 knockdown inhibited the proliferation, migration, and invasion of MH7A cells. The inhibitory effects of IGF2BP3 knockdown were effectively reversed by simultaneously overexpressing RRM2 in MH7A cells. By analyzing N6-methyladenosine (m6A)2Target database, five m6A regulatory target binding sites for IGF2BP3 were identified in RRM2 mRNA, suggesting a direct relationship between IGF2BP3 and RRM2 mRNA. Additionally, in RRM2 small hairpin (sh)RNA lentivirus-infected cells, the levels of phosphorylated Akt and MMP-9 were significantly decreased compared with control shRNA lentivirus-infected cells. The present study demonstrated that RRM2 promoted the Akt phosphorylation leading to high expression of MMP-9 to promote the migration and invasive capacities of MH7A cells. Overall, IGF2BP promotes the expression of RRM2, and regulates the migration and invasion of MH7A cells via Akt/MMP-9 pathway to promote RA progression.

Effects of Secukinumab on Enthesiophyte and Erosion Progression in Psoriatic Arthritis-A One-year Double-blind, Randomized, Placebo-controlled Trial Utilizing High-resolution Peripheral Quantitative Computed Tomography

Background This study aimed to ascertain the effect of secukinumab on erosion and enthesiophyte progression in psoriatic arthritis (PsA) by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods This was a one-year double-blind, randomized, placebo-controlled trial (NCT0362386740). Patients with erosion in the metacarpophalangeal joints (MCPJ) 2-4 were randomised in a 1:1 ratio to either the secukinumab or placebo group. HR-pQCT of the MCPJ 2-4 were performed at baseline, week-24 and 1-year. Progression of enthesiophyte were defined as changes in enthesiophyte volume exceeding smallest detectable change (SDC) (0.12mm3) or the identification of any new enthesiophyte. Partial repair of erosion was defined as a reduction in erosion volume greater than SDC (0.1mm3). Results Forty patients (age: 51.9± 13.4 years, 20 [50%] male) were recruited. Thirty-four patients who completed study treatment were included in the per-protocol analysis. The erosion volume at baseline, week-24 and week-48 revealed significant reduction in the secukinumab group while no differences in the placebo group (Figure-3A). There was a trend suggesting that fewer patients developed new-erosions in the secukinumab group (one-erosion in one-patient) compared to the placebo group (six-erosions in five-patients) (p=0.078) (Figure-3B). A significantly higher proportion of erosions with partial healing was observed in the secukinumab group compared with the placebo group [51%vs30%, p=0.029] (Figure-3C). Regarding enthesiophyte, a total of 25-enthesiophytes were identified in both the secukinumab and placebo groups at baseline. The enthesiophyte volume at baseline, week-24 and week-48 revealed significant differences in the secukinumab group while no differences in the placebo group (Figure-3D). While one (one-enthesiophyte in one-patient) and four-enthesiophytes (four-enthesiophytes in three-patients) were newly identified in the secukinumab group and placebo group respectively (Figure-3E), the proportion of enthesiophyte progression was numerically higher in the placebo group than the secukinumab group [40%vs16%, p=0.114] at week 48 (Figure-3F). GEE results showed that the odds ratio (OR) for enthesiophyte progression in the secukinumab group was 0.264 (95% CI: 0.080-0.878, p=0.030), while the OR for partial erosion healing in the secukinumab group was 2.816 (95% CI: 1.109 to 7.153, p=0.029), adjusting for tender-joint-counts. Conclusions Secukinumab demonstrates a potential benefit in facilitating partial erosion repair and preventing enthesiophyte progression in PsA.

The emerging role of neutrophil extracellular traps in the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. Neutrophil extracellular traps (NETs are NETwork protein structures activated by neutrophils to induce the cleavage and release of DNA-protein complexes). Current studies have shown the critical involvement of NETs in the progression of autoimmune diseases, Neutrophils mostly gather in the inflammatory sites of patients and participate in the pathogenesis of autoimmune diseases in various ways. NETs, as the activated state of neutrophils, have attracted much attention in immune diseases. Many molecules released in NETs are targeted autoantigens in autoimmune diseases, such as histones, citrulline peptides, and myeloperoxidase. All of these suggest that NETs have a direct causal relationship between the production of autoantigens and autoimmune diseases. For RA in particular, as a disorder of the innate and adaptive immune response, the pathogenesis of RA is inseparable from the generation of RA. In this article, we investigate the emerging role of NETs in the pathogenesis of RA and suggest that NETs may be an important target for the treatment of inflammatory autoimmune diseases.

Moderate and high disease activity levels increase the risk of subclinical atherosclerosis progression in early rheumatoid arthritis: a 5-year prospective study

ObjectivesTo elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA).MethodsThis was a 5-year prospective study. Patients with consecutive...

The Signature of Serum MicroRNA Folding Change in Rheumatoid Arthritis

BACKGROUND: A class of endogenous single-stranded short noncoding RNAs known as microRNAs (miRNAs) has become important epigenetic regulators of physiological and pathological processes in numerous disorders. They regulate the posttranscriptional expression of many genes to control basic cellular pathways and functions. Many research indicates that miRNAs play a role in the initiation and progression of rheumatoid arthritis (RA). OBJECTIVE: This study was comprehensively focused on the role of miRNA-146a and impaired cellular functions in RA. MATERIALS AND METHODS: A case–control study was conducted on a total of 90 samples, comprising 30 control samples and 60 RA patient samples. Samples of patients were chosen from the Imam Hassan al-Mujtaba Hospital located in Kerbala Governate. RNAClean XP Kit and an RNase-Free DNase Set were used to isolate and purify total RNA. Through statistical analysis, the receiver operating characteristic (ROC) curve was used to determine how effectively the predicted value worked. RESULTS: Patients with RA were shown an increasing level of the folding change of miRNA-146a when compared to the control groups. A comparison of serum level of miRNA-146a fold change in different body mass index (BMI) groups was also performed. The level of folding change was shown a massive increasing that was seen with increasing BMI. It was found that miRNA-146a and folding change were highly significant risk factors in RA. CONCLUSION: MiRNAs-164a may be an appealing alternative for usage as biomarkers in clinical applications such as prognosis and disease detection.

Midterm Clinical and Radiological Outcomes of Revision Lateral Meniscal Allograft Transplantation.

It is unknown whether the outcomes achieved in the early period after revision lateral meniscal allograft transplantation (RLMAT) are maintained through the midterm period. To evaluate the midterm clinical and radiological results of patients who underwent RLMAT. Case series; Level of evidence, 4. We reviewed the outcomes of 19 RLMATs in 18 patients with at least 5 years of follow-up data. The mean follow-up period was 6 ± 1.1 years (range, 5-8.5 years). Clinical outcomes were assessed using the modified Lysholm score, the International Knee Documentation Committee (IKDC) subjective score, and the Tegner activity level. Radiographic progression of arthritis was measured by the absolute and relative joint space widths on 45° of knee flexion posteroanterior radiographs preoperatively, 1 year postoperatively, and at the latest follow-up.Failure was defined as meniscocapsular separation, removal, or tear of more than half of the meniscal allograft on postoperative magnetic resonance imaging (MRI) or conversion to total knee arthroplasty. Of the 18 patients, 3 underwent ≥2 RLMATs. The survival rate was evaluated according to the number of revision surgeries. For knees with an intact meniscus transplant at the final follow-up, the modified Lysholm and IKDC scores were significantly improved compared with preoperatively, but the Tegner activity level was unchanged. No significant differences were found in the absolute and relative joint space widths postoperatively. There were 6 failures within 3 years after RLMAT; the overall 5-year survival rate was 68.4% (13/19 knees). All failed knees showed bucket-handle tear patterns on MRI due to meniscocapsular healing failure. The survival rate decreased as the number of RLMATs increased-73.3% for a first RLMAT (n = 15 knees), 66.7% for a second RLMAT (n = 3 knees), and 0% for a third RLMAT (n = 1 knee). Midterm MRIs of 8 well-healed RLMATs showed evidence of meniscal degeneration; nonetheless, this did not affect clinical outcomes. The midterm results of RLMATs demonstrated a 5-year survival rate of 68.4% and positive clinical and radiological outcomes for failed MATs despite unimproved activity levels. Inadequate meniscocapsular healing was the leading cause of failure, and it needs to be carefully considered when performing RLMATs.

Peptidase inhibitor 16 promotes inflammatory arthritis by suppressing Foxp3 expression via regulating K48-linked ubiquitin degradation Bmi-1 in regulatory T cells

Abnormalities of regulatory T cells (Tregs) has been suggested in rheumatoid arthritis (RA), and Forkhead box P3 (Foxp3) is the key transcriptional factor of Tregs expression. However, the underlying molecular mechanism remains unclear. Here, we demonstrated peptidase inhibitor 16 (PI16) was significantly increased in the peripheral blood, synovial fluid, and synovial tissue from RA patients. PI16 transgenic mice (PI16Tg) aggravated arthritis severity partly through suppressing Foxp3 expression. Mechanistically, PI16 could interact with and stabilize Bmi-1 in Tregs via inhibiting K48-linked polyubiquitin of Bmi-1, which promotes the enrichment of repressive histone mark in Foxp3 promoter. Furthermore, Bmi-1 specific inhibitor PTC209 could restore Foxp3 expression and alleviate arthritis progression in PI16Tg mice, accompanied by increased recruitment of active histone mark in the promoter of Tregs. Our results suggest that PI16-Bmi-1 axis plays an important role in RA and other autoimmune diseases by suppressing Foxp3 expression in Tregs via Bmi-1-mediated histone modification.

A Comparison of Rib Osteochondral Graft to Medial Femoral Trochlear Osteocartilaginous Graft for the Salvage of the Fragmented Scaphoid Proximal Pole: A Single-Center Experience with Minimum 2-Year Follow-Up.

Purpose Fragmented fractures of the proximal pole of the scaphoid that cannot be internally fixed may be salvaged by four-corner arthrodesis or proximal row carpectomy. Replacement of the proximal scaphoid with costal-osteochondral graft (COG) or the medial femoral trochlea (MFT) graft are two alternative solutions for this clinical presentation. The purpose of this study was to compare the clinical and radiographic results of the COG and the MFT graft with a minimum 2-year follow-up from a single centre. Methods A retrospective study was performed to investigate the outcome of COG and MFT with a minimum 2 year follow up. Demographic data and clinical assessment including wrist range of motion and grip strength measurements and Oxford Knee score were collected. Patients completed the outcome measures of Disabilities of Arm, Shoulder, and Hand (DASH), the Patient-Rated Wrist Evaluation (PRWE), and a ten-point visual analogue score for pain (VAS). Radiological examination was performed on all wrists at follow-up. Results The visual analogue score, DASH and PRWE were similar between the two groups. There was radiographic evidence of arthritis between the radial styloid and distal scaphoid in all patients that underwent COG but no evidence in those that underwent MFT graft reconstruction. There were different complications in each group. Thirty percent of patients that underwent MFT reconstruction had persistent knee pain at follow up. Conclusion Though there are notable differences in the follow-up period, patients undergoing MFT risk developing knee pain, while those undergoing COG risk radiographic progression of wrist arthritis. Level of Evidence III - Comparative study.