Osteoarthritis Levels Research Articles

The Role of Disease Severity, Affected Joints, and Physical Activity Levels on Functional Impairment in Osteoarthritis after the COVID-19 Pandemic

Hip and knee osteoarthritis (OA) is common among Chilean adults over 60, impacting their functionality. This study aimed to determine how health factors such as disease severity, type of OA, medication use, and physical activity levels relate to functionality in individuals with OA. The sample size included 67 women and 13 men aged 38 to 92 (66.6 ± 11.2) with diagnosed knee or hip OA. The International Physical Activity Questionnaire-Short Form (IPAQ-SF) was used to estimate physical activity, the Lequesne Index for functional impairment, and the VAS (Visual Analog Scale) for pain. Data were collected from December 2022 to March 2023. We performed bivariate analyses, which indicated that greater OA severity and bilateral OA are associated with increased functional impairment and pain. Medication use was correlated with higher pain levels, and physical activity was correlated with functionality; there was no correlation with age. Here, 65.4% of the variance in functionality problems was explained by OA severity, bilateral involvement, and pain level, highlighting their impact on functionality. Functionality problems were higher in individuals who suffered higher levels of severity when they performed lower levels of physical activity. These findings underscore the importance of promoting physical activity to improve the quality of life for individuals with OA.

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study

BackgroundPreventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2–5 years...

Platelet and Lymphocyte-Related Parameters as Potential Markers of Osteoarthritis Severity: A Cross-Sectional Study.

Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering age, sex, and body mass index (BMI). Patients aged ≥40 years were included in this cross-sectional study and divided into groups based on knee OA severity using the Kellgren-Lawrence (KL) grading system. A logistic regression model, adjusted for confounders, evaluated the ability of PLT, MPV, LINF, and PLR to categorize OA severity. Model performance in terms of accuracy, sensitivity, and specificity was assessed using ROC curves. The study involved 245 OA patients (51.4% female, 48.6% male) aged 40-90 years, 35.9% with early OA (KL < 3) and 64.1% moderate/severe OA (KL ≥ 3). Most patients (60.8%) were aged ≥60 years, and BMI was <25 kg/m2 in 33.9%. The model showed that a 25-unit increase in PLR elevates the odds of higher OA levels by 1.30 times (1-unit OR = 1.011, 95% CI [1.004, 1.017], p < 0.005), while being ≥40 years old elevates the odds by 4.42 times (OR 4.42, 95% CI [2.46, 7.95], p < 0.0005). The model's accuracy was 73.1%, with 84% sensitivity, 52% specificity, and an AUC of 0.74 (95% CI [0.675, 0.805]). Higher PLR increases the likelihood of moderate/severe OA, suggesting that monitoring these biomarkers could aid in early detection and management of OA severity. Further research is warranted to cross-validate these results in larger populations.

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation.

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague-Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.

Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. Level I.

Cartilage Oligomeric Matrix Protein in Osteoarthritis and Obesity-Do New Considerations Emerge?

The diagnosis of osteoarthritis (OA) is based on radiological changes that are delayed, along with clinical symptoms. Early and very early diagnosis at the stage of molecular pathology may eventually offer an opportunity for early therapeutic intervention that may retard and prevent future damage. Cartilage oligomeric matrix protein (COMP) is a non-collagenous extracellular matrix protein that promotes the secretion and aggregation of collagen and contributes to the stability of the extracellular matrix. There are contradictory literature data and currently, the parameter is used only for scientific purposes and its significance is not well-determined. The serum level of COMP in patients with metabolic type OA of the knee has not been evaluated. The aim of the study was to analyze serum COMP levels in metabolic knee OA and controls with different BMI. Our results showed that the mean COMP values were significantly higher in the control group (1518.69 ± 232.76 ng/mL) compared to the knee OA patients (1294.58 ± 360.77 ng/mL) (p = 0.0012). This may be related to the smaller cartilage volume in OA patients. Additionally, COMP levels negatively correlated with disease duration (p = 0.04). The COMP level in knee OA with BMI below 30 kg/m2 (n = 61, 1304.50 ± 350.60 ng/mL) was higher compared to cases with BMI ≥ 30 kg/m2 (n = 76, 1286.63 ± 370.86 ng/mL), but the difference was not significant (p = 0.68). Whether this finding is related to specific features in the evolution of the metabolic type of knee OA remains to be determined. Interestingly, comparison of COMP levels in the controls with different BMI revealed significantly higher values in overweight and obese individuals (1618.36 ± 203.76 ng/mL in controls with BMI ≥ 25 kg/m2, n = 18, 1406.61 ± 216.41 ng/mL, n = 16; p = 0.0092). Whether this finding is associated with increased expression of COMP in the adipose tissue or with more intensive cartilage metabolism in relation to higher biomechanical overload in obese patients, considering the earlier development of metabolic type knee OA as an isolated finding, remains to be determined.

Knee Measurement System with Osteoarthritis Levels Using Artificial Cartilage and Skeletons.

Knee osteoarthritis (OA), also known as degenerative arthritis, is a disease characterized by irreversible changes in the cartilage and bones comprising the joints, resulting in pain, impaired function, and deformity. Furthermore, independent of natural aging, the rate of change in joint cartilage has increased in recent years, which is mainly attributed to environmental factors. The rising incidence of knee-related disorders emphasizes the importance of analyzing the morphology and kinematics of knee structure. This study introduces a knee measurement system designed to replicate the motions of knee using 3D-printing technology, providing insights into knee mechanics with OA level. The research explores the stages of OA using the Kellgren-Lawrence (KL) grade scale, highlighting the variations in the force applied to the knee bone according to movement. The developed knee-simulation system, utilizing the four-bar-link theory, presents a novel approach to studying OA levels 0 to 4. As OA progresses, the cartilage deteriorates, affecting the movement of OA. The OA-based knee measurement system that incorporates soft tissues and skeletons can assist in developing a personalized diagnostic approach for knee disease. This will also help to enhance surgical effectiveness by facilitating the creation of personalized prosthetic joints for individual patients and offering a customized surgical simulation.

Prevalence of Knee OA and its Association with Low Back Pain

Background: Knee osteoarthritis (OA) is a prevalent musculoskeletal condition known to impact quality of life and daily functioning significantly. Previous studies have identified a potential association between knee OA and low back pain, but this relationship requires further exploration to understand its implications fully. Objective: The objective of this study was to investigate the correlation between knee OA and low back pain, specifically examining the impact of knee pain on quality of life, daily functioning, and the severity of low back pain. Methods: A cross-sectional study was conducted with 377 OA patients aged between 45 to 75 years, selected via non-probability convenient sampling from various hospitals in Sialkot. Exclusion criteria included a history of knee surgery or recent trauma, mental retardation, or diabetes. Data were collected using the Oswestry Low Back Disability Index and the KOOS Urdu version. Statistical analysis was performed using SPSS version 26, focusing on descriptive statistics, mean and standard deviation for quantitative data, and the chi-square test for associations, with a significance threshold set at a p-value greater than 0.05. Results: The study found that the prevalence of knee OA varied by age group, with the highest prevalence (46.6%) in the 45-54 age group. Female participants predominated (75.9%). Severity levels of knee OA were classified as mild (32.6%), moderate (42.2%), and severe (21.8%). Significant correlations were observed between knee OA and low back pain, with correlation coefficients of 0.480 for pain effects on QOL, 0.441 for pain during SRF, 0.571 for pain during AODL, and 0.437 for the total score of pain. Conclusion: The study confirms a significant correlation between knee OA and low back pain, highlighting the need for integrated management approaches for patients suffering from these conditions. Addressing both knee and back pain concurrently could lead to better patient outcomes and improved quality of life.

PREVALENCE AND EFFECTS OF PROGRESSIVE OSTEOARTHRITIS ON SEX STEROIDS IN MALE AND FEMALE PATIENTS OF DISTRICT BUNER, KPK PAKISTAN

Osteoarthritis is a major cause of disability in older people; pain is considered one of the most important signs of osteoarthritis, which normally affects the weight-bearing joint, especially the knee joint. The objective of the present study was to find out the prevalence and effects of progressive Osteoarthritis (OA) on sex steroids in male patients of district Buner KP, Pakistan. Data was collected from 294 OA patients (Male, 46.18%; Female, 54.76%) at different hospitals through questionnaires, face-to-face interviews and blood sampling in district Buner. Results showed that the 50 to 60-year age group was mostly affected by OA (29.81%). In the case of females, OA was common in the plain areas, while male patients were in hilly areas. Among 294 patients, housewives (23.46%) and agriculture (18.7%) are more affected by Osteoarthritis. Blood samples were collected from 18 male patients of different age groups and analysed through the ELISA (enzyme-linked immunosorbent Assay) Test. The results obtained from ELISA showed that most of the OA patients have normal testosterone levels, but the two age groups, i.e., 50 to 60 and 60 to 70, have abnormal results of 0.251 ng/ml and 1.89 ng/ml. After analysis of all testosterone test results at different age groups, analysis of variance (ONE WAY ANOVA) results show that SS, MS and F values were 36.30, 7.26 and 9.3, respectively. We concluded that people over 40 are more likely to get OA. Osteoarthritis is more common in women than males, and it is more common in overweight people. Mountainous locations have a higher incidence of males with OA than females. Additionally, there are more females than males in plain terrain. According to our findings, bilateral OA is more typical than unilateral OA. Our research indicates a tenuous connection between OA and male patients' testosterone levels.

The Significant Role of Alcohol in the Relationship between C-Reactive Protein and Self-Reported Osteoarthritis

BackgroundDespite the known inflammatory nature of osteoarthritis (OA) and the established role of C-reactive protein (CRP) as an inflammation marker, the influence of alcohol consumption on the CRP–OA relationship remains uncertain, with previous research providing conflicting results. ObjectivesThis study aims to examine the potential moderating effect of alcohol on the association between CRP concentrations and self-reported OA. MethodsWe conducted a cross-sectional study involving 50,259 participants, all data collected from NHANES between 2005–2010 and 2015–2018. A multivariable logistic regression model was used to analyze the relationship between CRP and OA. ResultsWe found a nonsignificant positive association between CRP concentration and prevalence of self-reported OA after adjusting for covariates in the raw dataset or 5 multiple imputed datasets. In the stratified analysis by alcohol drinking, for every 10 mg/L higher in CRP concentration, the prevalence of self-reported OA was higher by 13 % in nondrinkers (P = 0.007, adjusted for covariates). Conversely, for every 10 mg/L higher in CRP concentration, the prevalence of self-reported OA was lower by 59 % in drinkers (P = 0.005, adjusted for covariates). Furthermore, we discovered that the directions of the association between CRP concentrations (10 mg/L) and prevalence of self-reported OA [odds ratio (OR) < 1 in the drinking subgroup and OR > 1 in the no-drinking subgroup] were stable in both the main and sensitivity analyses. The significant interaction between CRP concentration and alcohol drinking on the prevalence of self-reported OA was shown in most of our analyses (P-interaction < 0.05). ConclusionAlcohol consumption may be an interaction factor between CRP and self-reported OA. To our knowledge, our findings are the first to highlight the importance of incorporating analysis of alcohol consumption differences into future studies of CRP and self-reported OA.

Lipocalin-2 Serum Levels in Rheumatoid Arthritis Patients Treated with Adalimumab and Its Correlation with Proinflammatory Factors.

Obesity is associated with an increased risk for different chronic diseases such as osteoarthritis (OA) or rheumatoid arthritis (RA). In fact, adipose tissue is now recognized as an endocrine organ able to secrete a wide variety of factors called adipokines, which have been demonstrated to participate in the pathophysiology of RA by regulating inflammation and immunity. LCN2 is one of these adipose tissue-derived factors. However, scarce information is available about the levels of this adipokine in different rheumatic diseases. Therefore, we aimed to analyze LCN2 serum levels in healthy, OA, and RA patients under different treatments. Serum levels of LCN2, among other proinflammatory and chemotactic factors, have been measured by ELISA or Multiplex in the following four groups of individuals: healthy, OA, and RA patients treated with conventional treatment or adalimumab. We found increased serum levels of LCN2 in OA and RA patients. Interestingly, LCN2 serum levels show a similar pattern to that observed for different proinflammatory and chemotactic factors, being increased in RA conventional treated patients in comparison to RA patients treated with adalimumab. Also, RA patients under conventional treatment revealed a positive and significant correlation between LCN2 and CCL2, CCL3, IL-8, IL-1β, IL-6, and CRP. In patients with RA treated with adalimumab, only IL-6 and CRP correlated significantly with LCN2. Our results clearly suggest that LCN2 is modulated and associated with inflammation in rheumatic diseases. Therefore, the serum levels of this adipokine might be used as an additional biomarker of the inflammatory/disease activity.

Bioinformatics and system biology analysis revealed the crosstalk between COVID-19 and osteoarthritis.

The global coronavirus disease 2019 (COVID-19) outbreak has significantly impacted public health. Moreover, there has been an association between the incidence and severity of osteoarthritis (OA) and the onset of COVID-19. However, the optimal diagnosis and treatment strategies for patients with both diseases remain uncertain. Bioinformatics is a novel approach that may help find the common pathology between COVID-19 and OA. Differentially expressed genes (DEGs) were screened by R package "limma."Functional enrichment analyses were performed to find key biological functions. Protein-protein interaction (PPI)network was constructed by STRING database and then Cytoscape was used to select hub genes. External data sets and OA mouse model validated and identified the hub genes in both mRNA and protein levels. Related transcriptional factors (TF) and microRNAs (miRNAs) were predicted with miRTarBase and JASPR database. Candidate drugs were obtained from Drug Signatures database. The immune infiltration levels of COVID-19 and OA were evaluated by CIBERSORT and scRNA-seq. A total of 74 common DEGs were identified between COVID-19 and OA. Receiver operating characteristiccurves validated the effective diagnostic values (area under curve > 0.7) of four hub genes (matrix metalloproteinases9, ATF3, CCL4, and RELA) in both the training and validation data sets of COVID-19 and OA. Quantitative polymerase chain reaction and Western Blot showed significantly higher hub gene expression in OA mice than in healthy controls. A total of 84 miRNAs and 28 TFs were identified to regulate the process of hub gene expression. The top 10 potential drugs were screened including "Simvastatin,""Hydrocortisone,"and "Troglitazone" which have been proven by Food and Drug Administration. Correlated with hub gene expression, Macrophage M0 was highly expressed while Natural killer cells and Mast cells were low in both COVID-19 and OA. Four hub genes, disease-related miRNAs, TFs, drugs, and immune infiltration help to understand the pathogenesis and perform further studies, providing a potential therapy target for COVID-19 and OA.

CD39+CD55- Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee.

Recent studies utilizing single-cell analysis have unveiled the presence of various fibroblast (Fb) subsets within the synovium under inflammatory conditions in osteoarthritis (OA), distinguishing them from those in rheumatoid arthritis (RA). Moreover, it has been reported that pain in knee OA patients is linked to specific fibroblast subsets. Single-cell expression profiling methods offer an incredibly detailed view of the molecular states of individual cells. However, one limitation of these methods is that they require the destruction of cells during the analysis process, rendering it impossible to directly assess cell function. In our study, we employ flow cytometric analysis, utilizing cell surface markers CD39 and CD55, in an attempt to isolate fibroblast subsets and investigate their relationship with OA pathology. Synovial tissues were obtained from 25 knee OA (KOA) patients. Of these, six samples were analyzed by RNA-seq (n = 3) and LC/MS analysis (n = 3). All 25 samples were analyzed to estimate the proportion of Fb (CD45-CD31-CD90+) subset by flow cytometry. The proportion of Fb subsets (CD39+CD55- and CD39-CD55+) and their association with osteoarthritis pathology were evaluated. CD39+CD55- Fb highly expressed myogenic markers such as CNN1, IGFBP7, MYH11, and TPM1 compared to CD39-CD55+ Fb. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of upregulated differentially expressed genes (DEGs) in CD39+CD55- Fb identified the Apelin pathway and cGMP-PKC-signaling pathway as possibly contributing to pain. LC/MS analysis indicated that proteins encoded by myogenic marker genes, including CNN1, IGFBP7, and MYH11, were also significantly higher than in CD39-CD55+ Fb. CD39-CD55+ Fb highly expressed PRG4 genes and proteins. Upregulated DEGs were enriched for pathways associated with proinflammatory states ('RA', 'TNF signaling pathway', 'IL-17 signaling pathway'). The proportion of CD39+CD55- Fb in synovium significantly correlated with both resting and active pain levels in knee OA (KOA) patients (resting pain, ρ = 0.513, p = 0.009; active pain, ρ = 0.483, p = 0.015). There was no correlation between joint space width (JSW) and the proportion of CD39+CD55- Fb. In contrast, there was no correlation between the proportion of CD39-CD55+ Fb and resting pain, active pain, or JSW. In conclusion, CD39+CD55- cells exhibit a myofibroblast phenotype, and its proportion is associated with KOA pain. Our study sheds light on the potential significance of CD39+CD55- synovial fibroblasts in osteoarthritis, their myofibroblast-like phenotype, and their association with joint pain. These findings provide a foundation for further research into the mechanisms underlying fibrosis, the impact of altered gene expression on osteoarthritic joints, and potential therapeutic strategies.

Knee osteoarthritis in the former elite football players and the ordinary population: a comparative cross-sectional study

ABSTRACT A cross-sectional case–control study compared subjective knee function, quality of life and radiographic knee osteoarthritis (OA) between 45 former elite football players and an age-matched general male population. Participants completed the Knee OA Outcome Score (KOOS), a quality-of-life assessment (EQ-5D-3 L) and standing knee radiographs. Among the players, 24 (53%) sustained at least one moderate or severe knee injury, while 21 (47%) did not recall any injury. Players with previous knee injuries reported significantly lower knee-specific and general quality-of-life scores (KOOS 69; EQ-5D-3 L 0.69 (0.2)) compared to the non-injured players (KOOS 92; EQ-5D-3 L 0.81 (0.2)) or the control population (KOOS 90; EQ-5D-3 L 0.83 (0.2)). The injured knees had higher radiographic OA Kellgren-Lawrence (KL) scale grades 1.7 (1.3) than the knees of the non-injured players 0.8 (1.0) or the control knees 0.8 (1.0) Former elite football players who had previously sustained a moderate or severe knee injury reported inferior knee function and lower quality of life. Injured knees had higher levels of radiographic OA. Non-injured players reported similar knee and general function and their knees had similar grades of OA to those in the control group. The defining moment for long-term knee preservation in football should be injury prevention protocols.

An injectable copolymer of fatty acids (ARA 3000 BETA) as a promising treatment for osteoarthritis

Osteoarthritis (OA) is the most prevalent rheumatic disease and a fast growing cause of disability. Current pharmacological treatments include antalgics and non-steroid anti-inflammatory drugs to control pain and inflammation as well as slow acting drugs such as intra-articular (IA) administration of hyaluronic acid. Oral supplementation or diet rich in polyunsaturated free fatty acids are proposed but evidence for benefit is still under debate. We here investigated the therapeutic potential of ARA 3000 BETA, an injectable copolymer of fatty acids, at the structural level in OA. Collagenase-induced osteoarthritis model was induced in C57BL/6 mice by collagenase injection into knee joint. Mice were treated with one or two IA or four intra-muscular injections (IM) of ARA 3000 BETA. At sacrifice, knee joints were recovered for cartilage analysis by confocal laser scanning microscopy (CLSM) and bone analysis by micro-computed tomography system. OA histological scoring was performed after safranin O/fast green staining. Histological analysis revealed a protective effect against cartilage degradation in treated knee joints after IM and IA administration. This was confirmed by CLSM with a significant improvement of all articular cartilage parameters, including thickness, volume and surface degradation whatever the administration route. A slight protective effect was also noticed on subchondral bone parameters and knee joint calcification after IM administration and to a lesser extent, two IA injections. We demonstrated the therapeutic efficacy of injectable ARA 3000 BETA in OA with a protection against cartilage and bone alterations providing the proof-of-concept that clinical translation might be envisioned to delay disease progression.

Causal associations between serum amino acid levels and osteoarthritis: a Mendelian randomization study

The association between serum amino acid (AA) levels and osteoarthritis (OA) risk remains unclear. We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effects of. serum AA levels on the OA risk by using summary-level genome-wide association study (GWAS) data. Inverse variance weighted (IVW) and Wald ratio were used as the main analysis.We also applied MR-Egger, Weighted median and Robust Adjusted Profile Score (MR.RAPS) methods. Heterogeneity and horizontally pleiotropic outliers were checked. The causal effects of AAs on early-onset all OA were explored. We also performed multivariable MR (MVMR) and conducted the bidirectional MR. The results suggested that genetically predicted alanine (Ala), tyrosine (Tyr) and isoleucine (Ile) levels were significantly associated with OA risk (e.g., association between Ala and hip/knee OA risk: OR = 0.82, 95% CI = 0.75 ∼ 0.90, p = 1.54E-05). The study yielded little evidence of associations between genetically predicted AA levels with early-onset all OA risk. When adjusting the BMI in the MVMR model, suggestive causal effects of Ala and Tyr were also identified, while the effects of Ile substantially attenuated with OA risk. No significant associations between OA and AA levels were observed after testing for bidirectionality. Some AAs, such as Ala, Tyr and Ile likely affects the OA risk especially at hip or knee joints. The findings highlight the important role that serum AAs might play in the development of OA and provided new treatment approaches to OA.

Gait Asymmetry Variation in Kinematics, Kinetics, and Muscle Force along with the Severity Levels of Knee Osteoarthritis.

Knee osteoarthritis (OA) patients exhibit greater gait asymmetry than healthy controls. However, gait asymmetry in kinematics, kinetics and muscle forces across patients with different severity levels of knee OA is still unknown. The study aimed to investigate the changes of gait asymmetry in lower limb kinematics, kinetics, and muscle force across patients with different severity levels of knee OA. This is a cross-sectional study. From January 2020 to January 2021, 118 patients with symptomatic and radiographic medial knee OA were categorized into three groups using the Kellgren and Lawrence scale (mild: grade 1 and 2, n=37; moderate: grade 3, n=31; severe: grade 4, n=50). During self-paced walking, marker trajectories and ground reaction forces data were recorded. Musculoskeletal simulations were used to determine gait kinematics, kinetics, and muscle force. One-way analysis of variance with Tukey's post-hoc test was used to evaluate group difference. Paired-sample t-test was used to compared the between-limb difference. In the Severe group, significantly greater asymmetry index in knee flexion/extension range of motion (45%) was observed with a greater value on the contralateral side (p < 0.01), compared to the Mild (15%) and Moderate (15%) groups. Significantly higher peak hip contact force (JCF) on the contralateral side was found in the Mild (more affected side: 3.80 ± 0.67 BW, contralateral side: 4.01 ± 0.58 BW), Moderate (more affected side: 3.67 ± 0.56 BW, contralateral side: 4.07 ± 0.81 BW), and Severe groups (more affected side: 3.66 ± 0.79 BW, contralateral side: 3.94 ± 0.64 BW) (p < 0.05). Significantly greater gluteus medius muscle force on the contralateral side was found in Mild (more affected side: 0.48 ± 0.09 BW, contralateral side: 0.52 ± 0.12 BW), Moderate (more affected side: 0.45 ± 0.10 BW, contralateral side: 0.51 ± 0.15 BW), and Severe groups (more affected side: 0.42 ± 0.15 BW, contralateral side: 0.47 ± 0.12 BW) (p < 0.05). The contralateral side showing significantly higher peak knee adduction moment and medial knee JCF was only observed in the Mild group (p < 0.05). Gait asymmetry in kinematics and muscle forces increased from mild to severe knee OA. Asymmetrical gait pattern tends to transfer loads from the more affected side to the contralateral side. Peak hip JCF and gluteus medius muscle force can be used to detect this asymmetrical gait pattern in patients with knee OA, regardless of severity levels.

Expression patterns of eight RNA-modified regulators correlating with immune infiltrates during the progression of osteoarthritis.

RNA modifications in eukaryotic cells have emerged as an exciting but under-explored area in recent years and are considered to be associated with many human diseases. While several studies have been published relating to m6A in osteoarthritis (OA), we only have limited knowledge of other kinds of RNA modifications. Our study investigated eight RNA modifiers' specific roles in OA including A-to-I, APA, m5C, m6A, m7G, mcm5s2U, Nm and Ψ together with their relationship with immune infiltration. RNA modification patterns in OA samples were identified based on eight-type RNA modifiers and their correlation with the degree of immune infiltration was also methodically investigated. Receiver operating characteristic curves (ROC) and qRT-PCR was performed to confirm the abnormal expression of hub genes. The RNA modification score (Rmscore) was generated by the applications of principal component analysis (PCA) algorithm in order to quantify RNA modification modes in individual OA patients. We identified 21 differentially-expressed RNA modification related genes between OA and healthy samples. For example, CFI, CBLL1 and ALKBH8 were expressed at high levels in OA (P<0.001), while RPUSD4, PUS1, NUDT21, FBL and WDR4 were expressed at low levels (P<0.001). Two candidate RNA modification regulators (WDR4 and CFI) were screened out utilizing a random forest machine learning model. We then identified two distinctive RNA modification modes in OA which were found to display distinctive biological features. High Rmscore, characterized by increased immune cell infiltration, indicated an inflamed phenotype. Our study was the first to systematically reveal the crosstalk and dysregulations eight-type of RNA modifications in OA. Assessing individuals' RNA modification patterns will be conductive to enhance our understanding of the properties of immune infiltration, provide novel diagnostic and prognostic biomarkers, and guide more effective immunotherapy strategies in the future.

Bioinformatics Prediction and Experimental Validation Identify a Novel Cuproptosis-Related Gene Signature in Human Synovial Inflammation during Osteoarthritis Progression.

Osteoarthritis (OA) is the one of most common joint diseases worldwide. Cuproptosis, which had been discovered lately, is a novel form of cell death induced by copper. Our purpose is to study the relationship between cuproptosis-related genes (CRGs) and inflammatory microenvironments in patients with OA and identify characteristic cuproptosis-related biomarkers. First, the combinatory analysis of OA transcriptome data from five datasets identified differentially expressed CRGs associated with OA. Then, we applied single-sample gene set enrichment analysis (ssGSEA) to evaluate immune-cell infiltration and immune-function levels in OA patients and normal controls, respectively. Hub CRGs for OA were mined based on the random forest (RF) model, and a nomogram prediction model was constructed based on them. In total, four differentially expressed CRGs were identified through bioinformatics analysis and confirmed by RT-qPCR. FDX1 and LIPT1 were expressed at a high level in OA, while DBT and DLST were expressed higher in the normal group. In total, 10 CRGs were found to be significantly correlated with immune landscape. Four hub CRGs were subsequently obtained by the RF analysis as potential biomarkers for OA. We constructed an OA predictive model based on these four CRGs (DBT, DLST, FDX1, and LIPT1).

Validation of Levels of Decorin as A Reliable Biomarker of Osteoarthritis: Comparison of Serum and Synovial Fluid Levels

Objective: The proteoglycan decorin, which plays an important part in the aetiology of osteoarthritis as well as a role in the binding of collagen, was the focus of this study's background information and objectives (OA). This investigation was carried out with the objectives of determining the levels of decorin in the blood and synovial fluid of patients who suffered from knee OA and determining whether or not these levels had a correlation with OA and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. Place of Study: Islam medical college Sialkot Duration: December 2021 to May 2022 Methods: In this prospective study, a total of 60 persons were enrolled in the study and control groups: 30 people with knee osteoarthritis and 30 people with other knee sjoint problems. For the purpose of determining how well the knee functions, the WOMAC score was utilised.Both the levels of decorin in the blood and the levels of decorin in the synovial fluid were analysed by means of an enzyme-linked immunosorbent assay (ELISA). We used a technique known as binary logistic regression, which contained both a single and a multi-categorical predictor, in order to evaluate the potential risk factors for OA. This allowed us to determine which characteristics would increase the likelihood of developing OA. Results: It was discovered that the levels of serum decorin in the group that was diagnosed with OA were statistically and considerably higher than the levels found in the group that acted as the control (P 0.001). There was not a significant difference in the amounts of decorin found in synovial fluid between those who had OA and the control group. WOMAC score (OR)=1.073, 95% confidence interval (CI): 1.032-1.116, P&lt;0 .001 This association between OA and high serum decorin levels was shown to be statistically significant (OR=1.114, 95%CI: 1.030–1.205, P=0.007). OA was demonstrated to be strongly linked with high serum decorin levels. There was shown to be a positive association between the levels of serum decorin and the WOMAC score in patients who had OA. Conclusions: An increase in serum decorin levels may be indicative of changes in the structure of the extracellular matrix.The fact that there is a positive connection between the serum decorin level and the WOMAC score lends credence to the previous assertion that this conclusion is correct. It was found that having a higher WOMAC score and having higher serum decorin levels are both risk factors associated with osteoarthritis (OA). On the other hand, there was no link found between osteoarthritis and the amount of decorin found in the joint fluid.