Osteoarthritis Patients Research Articles

Comparison of responders and nonresponders with knee osteoarthritis after transcranial direct current stimulation.

The study compared responders and nonresponders to transcranial direct current stimulation (tDCS) regarding clinical pain outcomes in knee osteoarthritis (OA) patients. Sixty participants received home-based active tDCS, and clinical pain outcomes were compared between responders and nonresponders. Latent class growth analyses classified 41 participants as responders and 19 as nonresponders. Responders showed significantly greater decreases in pain intensity from baseline to post intervention than nonresponders (p < .001). Participants with higher BMI (p = .02) and weight (p = .005) were more likely to respond, while no significant sociodemographic differences were found. Identifying characteristics of nonresponsive tDCS subgroups can tailor treatments for each group. www.clinicaltrials.gov identifier is NCT04016272.

Managing of Post-traumatic Knee Arthritis by Total Knee Arthroplasty: Case Report and Literature Review

Introduction: Post-traumatic knee osteoarthritis (PTOA) develops rapidly after injuries from sports, accidents, or falls. Unlike primary osteoarthritis, PTOA escalates quickly, causing severe joint damage and impairments. Early intervention is crucial to alleviate pain, restore function, and prevent further deterioration. Delayed treatment worsens symptoms and increases the need for invasive procedures like total knee arthroplasty (TKA). Case Presentation: A 29-year-old patient with a year of left knee pain, swelling, and difficulty straightening had no history of rheumatic or autoimmune diseases. Examination showed osteophytes, indicating osteoarthritis. He underwent TKA with no complications, achieving a satisfactory outcome: good range of motion, improved quality of life, and an Oxford Knee Score of 42. Discussion: PTOA typically follows trauma to the joint surface, with severity often correlating with the impact intensity. In this case, the patient’s rapid development of osteoarthritis, despite his young age and lack of pre-existing conditions, may suggest a genetic predisposition. Knee arthroplasty was chosen to restore function, aligning with research showing comparable outcomes for post-traumatic and primary osteoarthritis patients, though post-trauma cases can have higher complication rates due to comorbidities. Conclusion: Effective management of PTOA is crucial due to its rapid progression and significant impact on joint function and quality of life. Early intervention is key to preventing severe damage and reducing the need for invasive treatments. While TKA can be effective, its success depends on the severity of the condition. Timely management and preventive strategies are vital to improving outcomes and maintaining joint health. Keywords: post traumatic osteoarthritis, total knee arthroplasty, quality of life, early intervention, case report

Investigation of GPM6B as a novel therapeutic target in Osteoarthritis.

Osteoarthritis (OA) is the most common motor system disease in older people, characterized by a high incidence and significant social and economic burden. Women have a higher risk of OA, more severe clinical symptoms, and a higher rate of disabilities than men. However, the pathogenesis of OA remains unclear. Therefore, we screened for differentially expressed genes (DEGs) in OA patients of different sex and searched for new targets that may be involved in regulating the development of OA. The study compared the expression of DEGs in synovial fluid exosomes between male and female patients with OA through RNA sequencing combined with bioinformatics analysis using public data. To evaluate the screened DEGs, synovial tissue and fluid samples were obtained from patients with OA who underwent joint replacement surgery. SiRNA-mediated knockdown in vitro experiments were performed to investigate the role of glycoprotein membrane 6B (GPM6B). Meanwhile, GPM6B gene knockout mice were used to assess the in vivo pathological roles of GPM6B in OA. The results revealed that GPM6B is a potential target associated with OA. Immunofluorescence staining demonstrated that GPM6B was expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes in patients with OA. In vitro experiments confirmed that GPM6B knockdown can reduce the expression of inflammatory factors in primary FLS from patients with OA. Under inflammatory conditions, GPM6B knockdown can reduce the expression of matrix metalloproteinases as well as proliferation of FLS. In addition, using a destabilization of the medial meniscus-induced OA model, we revealed that GPM6B is associated with OA progression in mice. Thus, we provided evidence that GPM6B act as a new target associated with OA.

Probiotics' supplementation alleviates disease severity and improves postural balance by repairing intestinal leak in patients suffering from osteoarthritis: A double-blinded clinical trial.

Increased intestinal leakiness and associated systemic inflammation are potential contributors to osteoarthritis (OA) and postural imbalance in the geriatric population. To-date, no successful treatment to correct postural imbalance in OA is known. We aimed to explore the effects of a multistrain probiotic upon postural imbalance in OA-affected patients. In this randomized, double-blind trial with a placebo group, 147 patients suffering from knee OA (age-span = 64-75 years) were divided into placebo (n=75) and probiotics (n=72) study groups. Vivomix 112 billion, multistrain probiotic was given once a day for 12 weeks. The outcomes of study variables were determined first at baseline and later after 12 weeks of intervention. These were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee flexion range-of-movement (ROM), pain intensity by visual analogue scale (VAS), handgrip strength (HGS), gait speed, and balance control assessed in standing, semi-tandem, and tandem stances. We determined plasma zonulin, to determine intestinal leak along with c-reactive protein (CRP) and 8-isoprostanes levels. A total of 136 OA patients taking placebo (n=71) and probiotics (n=65) were analyzed. The probiotics group exhibited a reduction in pain intensity, disease severity, and WOMAC scores along with improvement in balance scores, HGS, and walking speed (p<0.05 for all), no change in ROM, resting pain, and 8-isoprostanes levels. The correlation analysis revealed a robust association of balance scores with plasma markers of intestinal leakiness and inflammation in probiotics but not in the placebo group. Probiotics reduce postural imbalance in OA patients partly due to a reduction in intestinal leakiness.

Inhibition of Slit3/Robo1 signaling alleviates osteoarthritis in mice by reducing abnormal H-type vessel formation in subchondral bone

Background The aberrant H-type vessel formation was found to be intimately linked to subchondral bone remodeling during osteoarthritis (OA) development. Herein, we investigated the role and mechanism of osteoblast-secreted slit guidance ligand 3 (Slit3) in H-type vessel formation during OA progression. Methods Slit3 protein levels in subchondral bone samples of OA patients were detected. The isolated osteoblasts were transfected with Slit3 overexpression or knockdown plasmids, and their conditioned medium was cultured with endothelial progenitor cells (EPCs). The migration, tube formation, VEGF, and H-type vessel marker protein CD31 and endomucin (EMCN) levels in EPCs were accessed. The interactions between Slit3 and roundabout (Robo) family members were validated by Co-IP assay. Besides, whether the Slit3/Robo signaling affects the transforming growth factor β1 (TGF-β1)/SMADs pathway was determined. Additionally, sh-Slit3 was injected into OA mice, followed by the detection of articular cartilage degradation, subchondral bone remodeling, and H-type vessel formation. Results Slit3 was upregulated in subchondral bone tissues of OA patients. Slit3 overexpression in osteoblasts intensified the migration and H-type vessel formation of EPCs, while Slit3 knockdown showed the opposite results. Slit3 overexpression enhanced Robo1 protein level. Robo1 knockdown abrogated Slit3-mediated migration and H-type vessel formation in EPCs. Slit3 activated the TGF-β1/SMADs pathway in EPCs, which might be associated with H-type vessel formation in EPCs. Additionally, Slit3 silencing restrained articular cartilage degradation, aberrant subchondral bone formation, and H-type vessel formation in OA mice. Conclusion Inhibition of Slit3/Robo1 signaling alleviates osteoarthritis in mice by reducing abnormal H-type vessel formation in the subchondral bone.

Management of knee osteoarthritis using bone marrow aspirate concentrate: a systematic review.

Knee osteoarthritis (OA) is a common degenerative joint condition and a major cause of disability in the general population. Recent published literature identified from PubMed, EMBASE, Google Scholar, and Scopus. Orthobiological therapies try to regenerate articular cartilage and stop the progression of the degenerative lesion. Intra-articular injections of biological derivates have been increasingly used in the last decade. The indications for the use of bone marrow aspirate concentrate (BMAC) are still unclear. We systematically reviewed the current literature on BMAC in the management of knee OA, giving an update on the current indications for the selection of the ideal patient and the preparations and efficacy of BMAC compared to other biological alternatives. BMAC is a valuable source of mesenchymal stem cells, offering potential benefits in attenuating the inflammatory pathway associated with knee OA. Intra-articular injection of BMAC has shown effectiveness in clinical trials improving functional outcomes of knee OA patients. The superiority of BMAC over other orthobiological treatments cannot be assessed because of conflicting results.

Predictive analysis of osteoarthritis and chronic pancreatitis comorbidity: complications and risk factors

BackgroundThe comorbidity of chronic pancreatitis (CP) in patients with osteoarthritis (OA) is insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of CP in OA patients, as well as associated complications.MethodsA cohort of 181 patients was categorized into four groups: a control group (n=30), patients with OA (n=68), patients with CP (n=31), and patients with OA and comorbid CP (n=52). All four groups had no statistical differences in age and gender. The study utilized the WOMAC index, Visual Analog Scale (VAS), Lequesne index, biochemical assays, and advanced statistical methods to assess joint status in OA patients with comorbid CP. It explored potential predictors of comorbidity development and associated complications.ResultsThe study revealed that concurrent CP in OA exacerbates progression and contributes to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for CP comorbidity development in OA patients. Factors such as the WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxyvitamin D3, and BMI were found to influence the development of comorbidity of CP in OA. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation Syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency Domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors comorbidity CP with exocrine pancreatic insufficiency in OA patients.ConclusionThe presence of CP in OA patients exacerbates disease progression and complications, necessitating further investigation.

Therapeutic Controlled Release Strategies for Human Osteoarthritis.

Osteoarthritis is a progressive, irreversible debilitating whole joint disease that affects millions of people worldwide. Despite the availability of various options (non-pharmacological and pharmacological treatments and therapy, orthobiologics, and surgical interventions), none of them can definitively cure osteoarthritis in patients. Strategies based on the controlled release of therapeutic compounds via biocompatible materials may provide powerful tools to enhance the spatiotemporal delivery, expression, and activities of the candidate agents as a means to durably manage the pathological progression of osteoarthritis in the affected joints upon convenient intra-articular (injectable) delivery while reducing their clearance, dissemination, or side effects. The goal of this review is to describe the current knowledge and advancements of controlled release to treat osteoarthritis, from basic principles to applications in vivo using therapeutic recombinant molecules and drugs and more innovatively gene sequences, providing a degree of confidence to manage the disease in patients in a close future.

Interconnected Pathways: Exploring Inflammation, Pain, and Cognitive Decline in Osteoarthritis

The relationship among inflammation, pain, and cognitive decline in osteoarthritis (OA) patients is complex and has not been sufficiently explored; therefore, we undertook this research to evaluate how OA-related inflammation and pain affect cognitive functions, as well as to examine the potential of urinary markers as indicators of these conditions. This study examined fifty OA patients through clinical and cognitive assessments, morphological analyses, urinary biomarkers, and bioinformatics. Morphologically, 24% of patients had moderate to high synovial inflammation, which was significantly correlated with depressive symptoms, pain intensity, and self-reported anxiety. The Montreal Cognitive Assessment indicated minimal decline in most patients but showed negative correlations with age and inflammation severity. Urinary TNF-α and TGF-β1 levels positively correlated with body mass index and pain and synovitis score and immune cell infiltration, respectively. In contrast, cartilage oligomeric matrix protein and C-telopeptides of type II collagen showed inverse correlations with pain duration and cognitive function, respectively. Distinct patient clusters with higher inflammation were identified and were associated with reported pain and depressive symptoms. Urinary TNF-α and TGF-β1 can serve as biomarkers reflecting inflammation and disease severity in OA. This study suggests that synovial inflammation may be linked to mental and cognitive health in some patient cohorts.

The role of lncRNA TSIX in osteoarthritis pathogenesis: mechanistic insights and clinical biomarker potential

BackgroundThis study seeks to elucidate the expressions of lncRNA TSIX in Osteoarthritis (OA) and to explore its mechanisms in regulating OA progression.MethodsRT-qPCR was employed to analyze the expression of TSIX in OA patients classified by Kellgren-Lawrence (K-L) grades. Receiver operator characteristic (ROC) was conducted to evaluate the diagnostic value of TSIX. Correlation between TSIX levels and clinical scores such as Lysholm and visual analogue scale (VAS) score was evaluated using Pearson method. IL-1β-induced SW1353 cells served as an in vitro model. The cell function were assessed by flow cytometry and cell counting kit-8 (CCK-8) assay. The relationship between TSIX and miR-320a was verified by luciferase reporting system, while bioinformatics approaches were utilized to predict the downstream target genes of miR-320a.ResultsThe findings revealed that TSIX level in OA patients was elevated compared to that of the control group, with a notable progressive increase in TSIX expression correlated with higher K-L grades. In OA patients, the Lysholm score showed a negative correlation with TSIX expression, while the VAS score displayed a positive correlation with TSIX levels. Cell studies demonstrated that inhibition of TSIX enhanced cell viability and mitigated IL-1β-induced apoptosis by targeting miR-320a, in addition to promoting Aggrecan and Collagen II secretion. Luciferase reporter assay further validated the targeting interaction among TSIX, miR-320a, and PTEN.ConclusionsThis study demonstrated an increased expression of TSIX in OA patients. It suggests that TSIX may play a role in chondrocyte dysfunction during OA by modulating the miR-320a/PTEN axis.

β-hydroxybutyrate ameliorates osteoarthritis through activation of the ERBB3 signaling pathway in mice.

The ketogenic diet (KD) has demonstrated efficacy in ameliorating inflammation in rats with osteoarthritis (OA). However, the long-term safety of the KD and the underlying mechanism by which it delays OA remain unclear. We found that while long-term KD could ameliorate OA, it induced severe hepatic steatosis in mice. Consequently, we developed two versions of ketogenic-based diets: KD supplemented with vitamin D and intermittent KD. Both KD supplemented with vitamin D and intermittent KD effectively alleviated OA by significantly reducing the levels of inflammatory cytokines, cartilage loss, sensory nerve sprouting, and knee hyperalgesia without inducing hepatic steatosis. Furthermore, β-hydroxybutyrate (β-HB), a convenient energy carrier produced by adipocytes, could ameliorate OA without causing liver lesions. Mechanistically, β-HB enhanced chondrocyte autophagy and reduced apoptosis through the activation of Erb-B2 receptor tyrosine kinase 3 (ERBB3) signaling pathway; a pathway which was down-regulated in the articular chondrocytes from both OA patients and mice. Collectively, our findings highlighted the potential therapeutic value of β-HB and KD supplemented with vitamin D and intermittent KD approaches for managing OA.

Exploring the Impact of Instrument-Assisted Soft Tissue Mobilization on Functional Measures and Quality of Life in Knee Osteoarthritis Patients: A Randomized Controlled Trial

Background: Knee osteoarthritis (KOA) is a prevalent disabling condition characterized by pain, stiffness, and functional limitations, significantly impacting quality of life, particularly among older adults. Instrument-assisted soft tissue mobilization (IASTM) is a technique that has shown promise in reducing pain and increasing the range of motion. Objectives: This study aimed to investigate the effects of IASTM on functional measures and quality of life in KOA patients. Methods: Thirty participants with unilateral KOA were randomized into IASTM and sham groups. The intervention consisted of four sessions over two weeks, combining IASTM with exercise therapy. Functional performance was assessed using the 6-minute walking test (6MWT) and the timed up and go test (TUG). Quality of life was evaluated using the 36-item short-form health survey (SF-36) and the Lequesne Algofunctional Index (LAI) Questionnaires. Results: A mixed ANOVA revealed significant improvements in functional performance in both groups after treatment in the 6MWT (P &lt; 0.001) and TUG (P = 0.003) tests. Significant improvements were observed in the SF-36 subgroups for physical functioning (P = 0.002), role limitations due to physical problems (P &lt; 0.001), energy/vitality (P &lt; 0.001), pain (P &lt; 0.001), and total score (P &lt; 0.001). There was also a significant time*group interaction effect for role limitations due to emotional problems (P = 0.005), with the IASTM group showing improvement after treatment while the sham group experienced a decline. The LAI questionnaire also indicated significant improvements in both groups (P &lt; 0.001) after treatment. Conclusions: Both IASTM and sham interventions, combined with exercise therapy, led to improvements in functional measures and quality of life. However, the IASTM group exhibited a more pronounced positive trend in the 6MWT and TUG tests, as well as a significant interaction effect for emotional role limitations. These findings suggest that while exercise alone can improve function and quality of life, the addition of IASTM may further enhance these outcomes, supporting its integration into KOA management strategies to improve activities of daily living and overall quality of life.

Impact of Structural Severity on Outcomes in Knee Osteoarthritis: An Analysis of Data from Phase 2 and Phase 3 Lorecivivint Clinical Trials.

Developing knee osteoarthritis (OA) treatments is challenging due to assessing pain and joint structure outcomes within a highly heterogeneous disease. Lorecivivint (LOR), an intra-articular (IA) CLK/DYRK inhibitor, modulates Wnt and inflammatory pathways. This review analysis of LOR 0.07 mg trial data aims to describe the potential impact of baseline joint structure on OA pain response. Two Phase 2 and two Phase 3 trials enrolled knee OA patients with Kellgren-Lawrence (KL) Grades 2-3 and Pain Numeric Rating Scale (NRS [0-10]) ≥4 to ≤ 8 in target knee. Cumulative frequency distribution plots by KL grade summarized the percentages of patients with medial joint space width (medial JSW) < 3 mm. Osteoarthritis Research Society International Joint Space Narrowing grades and treatment responses in trials capturing Pain NRS were similarly summarized. Pain outcome changes were estimated using baseline adjusted ANCOVA. Compared with phase 2 trials, the phase 3 trials had an increased proportion of patients with baseline medial JSW < 3 mm. LOR demonstrated beneficial treatment effects vs placebo in KL 2 subgroups, which were found to have higher proportions of baseline medial JSW > 3 mm, apart from one Phase 3 trial with advanced structural knee OA. Baseline medial JSWs were heterogeneous across trials despite KL inclusion criteria. LOR demonstrated greater symptomatic improvements in patients with less structurally advanced disease, indicative of an association between OA structural damage and pain. Early treatment interventions may improve outcomes and provide insight for future OA trial inclusion criteria development. OA-02, NCT02536833; OA-04, NCT03122860; OA-10, NCT04385303; OA-11, NCT03928184.

Intramuscular methylprednisolone in hand osteoarthritis: a retrospective cohort study

Abstract Objectives To explore patient characteristics associated with response to intramuscular methylprednisolone (MP) therapy in hand osteoarthritis (OA). Methods We performed an exploratory monocentric retrospective study. Patients with a clinical diagnosis of hand OA who visited our outpatient clinic between July 2016 and June 2021, and received at least once an intramuscular MP injection, were included. Clinical data, including laboratory and radiologic results, were retrieved from electronic patient records (EPRs). Patients’ reported response to MP and its duration in the first six months after injection was based on free text from the EPRs. Response was categorized into three groups: no response or worsening of symptoms, modest response, and good response. Duration of response was categorized as short-term (&amp;lt;2 weeks), or long-term (≥2 weeks). Multivariable logistic regression models were performed to determine factors associated with good response to therapy with methylprednisolone. Results Data from 262 hand OA patients (76% female) were analyzed. A good response was experienced by 150 patients (57.2%). Among those with modest to good response, the perceived response of 162 patients (80.6%) lasted 2 weeks or longer. Univariate regression analysis indicated that the level of CRP was associated with good response (odds ratio(OR) 1.08; 95% CI 1.00 to 1.17). However, multivariate regression analysis showed no statistical significant associations. Conclusion In this retrospective study, more than half of hand OA patients displayed good response to intramuscular MP administration. The possible relation between the presence of low-grade inflammation and the response to this therapy warrants further investigation.

Association between dietary omega-3 fatty acid intake and all-cause mortality in patients with osteoarthritis: a population-based prospective cohort study

A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.

The Efficacy and Safety of Green-Lipped Mussel Extract Plus Ginkgo Biloba on Anti-Inflammatory Status in Patients with Knee Osteoarthritis

Background: Clinical research on the efficacy of nutraceutical compounds recommended for the relief of osteoarthritis (OA) symptoms has been largely disputed. In addition, no link has been established between its safety and efficacy in Kurdish population. The aim of this study is to determine the efficacy of New Zealand green-lipped mussel extract + Ginkgo biloba (GLME+) in patients with OA, and analyze the effect of GLME+ on inflammation. Methods: In an open-label, single-group allocation study, 40 patients diagnosed with knee OA were administrated 1000 mg/day of New Zealand green-lipped mussel extract and 100 mg/day of Ginkgo biloba for eight weeks. The outcome measure was scored using Western Ontario and McMaster Universities arthritis index (WOMAC). The serum concentration of inflammatory chemokine (CCL3) and myeloperoxidase (MPO) were measured. An intention-to-treat analysis was employed and subject data at T0 and T8 weeks. Results: Results showed a significant improvement in WOMAC score in post-treated OA patients with GLME+ (P&lt;0.001). In addition, CCL3 serum levels were significantly decreased after an 8-week intervention (P&lt;0.001). Moreover, no statistical significance was observed within groups in MPO serum levels (P&gt; 0.05). Conclusions: GLME+ improved knee joint pain, stiffness, and mobility in OA patients. Two of GLME+'s chondroprotective properties were the reduction of oxidative damage and the inhibition of inflammation, both of which have been linked to the etiology of OA cartilage destruction. The findings indicated that GLME+ may be useful in the treatment of OA patients.

Consideration of the EXiLE test for predicting anaphylaxis after diclofenac etalhyaluronate administration

Diclofenac etalhyaluronate, an active pharmaceutical ingredient in JOYCLU® (JCL), serves as a joint function improvement agent in knee and hip osteoarthritis patients. However, frequent cases of anaphylaxis induced by JCL administration have been reported. Recent clinical research suggests the potential utility of the basophil activation test (BAT) in predicting JCL-induced anaphylaxis. Nonetheless, the BAT is deemed impractical for routine diagnostic testing due to complex procedures involving whole blood stimulation and flow cytometry-based analyses. In the study reported here, an IgE crosslinking-induced luciferase expression (EXiLE) test which uses patient sera without complicated procedures, was performed with patients who had received JCL, with or without subsequent anaphylactic symptoms. The results of this test were then compared with those of the BAT reported in a clinical research study. Of the six BAT-positive JCL-induced anaphylaxis-experienced patients, four were positive in the EXiLE test and all non-experienced patients were negative in both the BAT and EXiLE tests, thus illustrating a high concordance rate of 92.3%. Further validation of testing conditions is expected to improve these rates. Notably, complement inactivation treatment led to a positive EXiLE result in a BAT-negative patient. In conclusion, it appears that the EXiLE test exhibits promise as an alternative to BAT for predicting JCL-induced anaphylaxis, and in so doing offers a simpler diagnostic approach.

Exploring the role of the built environment and psychosocial mediators on knee function in knee osteoarthritis patients in Singapore: a cross-sectional study.

(1) To examine if a more accessible built environment (BE) is significantly associated with better knee function outcomes in knee osteoarthritis (OA) patients. (2) To assess if the relationship between BE and knee function is mediated by fear of movement and self-efficacy. Cross-sectional study. Two tertiary hospitals in Singapore. 212 knee OA patients (mean: 63.81±8.27 years old), majority female (69.8%). (i) meets National Institute for Health and Care Excellence criteria for knee OA, (ii) independent community ambulant. (i) alternative diagnosis to knee OA, (ii) secondary osteoarthritis, (iii) severe medical and/or cognitive comorbidity impairing activities of daily living, (iv) previous knee arthroplasty, (v) wheelchair bound, or (vi) pregnant. PRIMARY AND SECONDARY OUTCOME MEASURES; STATISTICS: How self-efficacy (Arthritis Self-Efficacy Scale-8 (ASES-8)) and fear of movement (Brief Fear of Movement (BFOM)) mediates impact of overall BE (IPAQ-Environment module: Access to Destinations) and five item-specific domains of BE accessibility on knee function (Knee Injury and Osteoarthritis Outcome Score-12 (KOOS-12)). For variables significantly correlated with BE and KOOS-12 in bivariate Pearson correlation tests, mediation analysis was performed with confounders adjusted. Total BE (r=0.142, p=0.038) and accessibility to transit station (r=0.161, p=0.019) were positively correlated with KOOS-12. Structural barriers (r=-0.138, p=0.045) were negatively correlated with KOOS-12. ASES-8 was a significant mediator in the relationship between accessibility to transit station and KOOS-12 (coeff=0.87, 95% CI=(0.24, 1.69), p=0.005) and between total BE and KOOS-12 (coeff=0.25, 95% CI=(0.10, 0.45), p=0.004). BFOM was a marginally significant mediator between structural barriers and KOOS-12 (coeff=-0.36, 95% CI=(-0.86, -0.02); p=0.054). More accessible BE and lesser structural barriers in the BE are associated with better knee function. Self-efficacy mediates the relationship between overall BE accessibility and knee function. Fear of movement mediates the negative association between barriers in the BE and knee function.Applications include assessing BE barriers and psychosocial mediators in clinician consultations, developing multidisciplinary integrated care models and urban designers planning mobility friendly BEs. The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

Multi-omics Data Integration Analysis Identified Therapeutic Targets and Potential Reuse Drugs for Osteoporosis.

To facilitate drug discovery and development for the treatment of osteoporosis. With global aging, osteoporosis has become a common problem threatening the health of the elderly. It is of important clinical value to explore new targets for drug intervention and develop promising drugs for the treatment of osteoporosis. To understand the major molecules that mediate the communication between the cell populations of bone marrow-derived mesenchymal stem cells (BM-MSCs) in osteoporosis and osteoarthritis patients and identify potential reusable drugs for the treatment of osteoporosis. Single-cell RNA sequencing (scRNA-seq) data of BM-MSCs in GSE147287 dataset were classified using the Seurat package. CellChat was devoted to analyzing the ligand-receptor pairs (LR pairs) contributing to the communication between BM-MSCs subsets. The LR pairs that were differentially expressed between osteoporosis samples and control samples and significantly correlated with immune score were screened in the GSE35959 dataset, and the differentially expressed gene in both GSE35959 and GSE13850 data sets were identified as targets from a single ligand or receptor. The therapeutic drugs for osteoporosis were screened by network proximity method, and the top-ranked drugs were selected for molecular docking and molecular dynamics simulation with the target targets. Twelve subsets of BM-MSCs were identified, of which CD45-BM-MSCS_4, CD45-BM- MSCS_5, and CD45+ BM-MSCs_5 subsets showed significantly different distributions between osteoporosis samples and osteoarthritis samples. Six LR pairs were identified in the bidirectional communication between these three BM-MSCs subsets and other BM-MSCs subsets. Among them, MIF-CD74 and ITGB2-ICAM2 were significantly correlated with the immune score. CD74 was identified as the target, and a total of 48 drugs targeting CD47 protein were identified. Among them, DB01940 had the lowest free energy binding score with CD74 protein and the binding state was very stable. This study provided a new network-based framework for drug reuse and identified initial insights into therapeutic agents targeting CD74 in osteoporosis, which may be meaningful for promoting the development of osteoporosis treatment.

Enhancing intrinsic TGF-β signaling via heparan sulfate glycosaminoglycan regulation to promote mesenchymal stem cell capabilities and chondrogenesis for cartilage repair

Osteoarthritis burdens patients due to the limited regenerative capacity of chondrocytes. Traditional cartilage repair often falls short, necessitating innovative approaches. Mesenchymal stem cells (MSCs) show promise for regeneration. Heparan sulfate glycosaminoglycans (HS-GAGs) regulate cellular functions, making them a target for cartilage repair. This study highlights how Heparinase III (HepIII) cleaves intact HS-GAGs in bone marrow-derived MSCs (BM-MSCs), enhancing their capabilities and specifically promoting chondrogenesis. HepIII-treated BM-MSCs cultured in a hanging drop device for three days, significantly increased cell number and aggregation into a cell sphere with early chondrogenesis. HepIII promoted BM-MSCs toward chondrogenesis, increasing type II collagen, intact HS-GAGs, and sulfated GAG content, while upregulating chondrogenic and heparan sulfate proteoglycan genes. Treatment with the TGF-β inhibitor (SB-431542) in HepIII-treated BM-MSCs demonstrated enhanced intrinsic transforming growth factor-β (TGF-β) signaling and fibronectin expression. This approach also boosted BM-MSC self-renewal, immunosuppressive potential, and modified acetylated histone signatures, offering a cost-effective strategy for cartilage repair by addressing inflammation, metabolic changes, and the high costs of traditional TGF-β methods. From the results, HepIII-treated BM-MSCs show potential for use in combination with other biopolymers as injectable gels to improve cartilage repair in osteoarthritis patients in the near future.