Ginger-derived nanovesicles attenuate osteoarthritis progression by inhibiting oxidative stress via the Nrf2 pathway.

Aim: Osteoarthritis (OA) is a common degenerative joint disease. Previous studies demonstrated ginger-derived exosome-like nanovesicles (GDN) showed therapeutic effects in degenerative diseases. However, it remains unknown whether GDN could alleviate OA progression.Materials & methods: In this study, GDN were obtained and characterized. Then we evaluated the effects of GDN in tert-butyl hydroperoxide (TBHP)-induced chondrocytes, posttraumatic OA rat model and ex vivo cultured human OA cartilage explants.Results: We demonstrated GDN promoted cartilage anabolism and alleviated oxidative stress in TBHP-induced chondrocytes and OA rat. Our results also showed GDN exhibited protective effects in cultured cartilage explants. Furthermore, we verified the Nrf2 pathway was associated with protective effects of GDN.Conclusion: Altogether, our findings demonstrated GDN hold great potential for OA treatment.

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mTORC2 inhibition by JR-AB2-011 improves IL-1ß-induced inflammation, catabolic response, and apoptosis in human chondrocytes through IκB-α/NF-κB p65.

Osteoarthritis (OA) is a very common chronic joint condition marked by inflammation and cartilage loss. mTOR is a well-known mediator of inflammation, cell survival, and aging; however, its role in OA has not been determined. To explore the role of mTORC2 in OA-and associated pathological changes, we examined the contribution of mTORC2-mediated Akt, rictor and IκB-α/NF-κB p65 pathway in interleukin (IL)-1ß-treated human chondrocytes. We focused on the protein expression of proinflammatory cytokines and catabolic and apoptotic factors, including TNF-α, IL-6, iNOS, MMP13, Bax, and caspase3, which may occur through this signalling pathway in IL-1ß-treated chondrocytes. Chondrocytes were cultured and treated with either 2 ng/mL IL­1ß alone or in combination with increasing concentrations of JR-AB2-011 (50, 100, or 250 µM), a selective mTORC2 inhibitor. The protein levels of phosphorylated (p)­Akt, Akt, rictor, p-NF-κB p65, NF-κB p65, IκB-α, p-IκB-α, iNOS, MMP13, Bax, and caspase3 were evaluated by Western blotting. In IL-1ß-stimulated chondrocytes, mTORC2 activity was increased with increased phosphorylation of Akt and expression of rictor. IL-1ß increased the expression of p-IκBα, p-NF-κB p65, NF-κB p65, IL-6, TNF-α, iNOS, Bax, and caspase3 proteins and decreased the expression of IκB-α. All of these IL-1ß-induced alterations were prevented by JR-AB2-011. The main novel finding in the present study is that selective mTORC2 inhibition by JR-AB2-011 prevents the inflammatory, catabolic, and apoptotic responses induced by IL-1ß via modulation of IκB-α/NF-κB activity. Therefore, we demonstrated a previously unknown function of mTORC2 inhibition that seems to be a potential therapeutic target for OA.

Genetic association of gut microbiota with osteoarthritis: a multivariable Mendelian randomization study considering medication use.

Background. The interplay among human gut microbiota (GM) composition, osteoarthritis (OA) and OA-related medication use has been extensively discussed. However, to date, there has been no exploration of the genetic correlation among these three factors.Hypothesis/Gap. The potential causal link between GM and OA), and whether medications influence this relationship, remains unclear.Methods. We utilized bidirectional Mendelian randomization (MR) to explore the genetic associations between GM and OA. We leveraged genome-wide association study (GWAS) summary statistics from the MiBioGen and GO consortia, which provided data on GM taxa and OA cases, respectively. We identified outlier single-nucleotide polymorphisms using radial-MR and assessed causal associations using inverse variance weighting (IVW), weighted median and MR-Egger methods. Robust outcomes, consistent across these methods, were reported. We addressed potential biases through tests for horizontal pleiotropy and heterogeneity, supplemented by the Mendelian randomization pleiotropy residual sum and outlier method. Multivariable MR techniques were applied to adjust for OA medication use using UK Biobank data.Results. IVW estimates revealed a significant increase in hip OA risk for Gordonibacter and Eubacterium (brachy group) [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.04-1.15, P=7.82E-04; OR: 1.09, 95% CI: 1.03-1.16, P=4.67E-03, respectively]. Conversely, Senegalimassilia, Slackia and Streptococcus exhibited protective effects (OR: 0.88, P=2.14E-02; OR: 0.88, P=3.33E-02; 0.91, P=4.29E-02). Sutterella increased the risk of knee OA (OR=1.15, 95% CI: 1.07-1.25, P=4.06E-04), while Haemophilus decreased it (OR=0.94, 95% CI: 0.88-1.00, P=4.26E-02). No significant heterogeneity or horizontal pleiotropy was observed in the results. Even after accounting for the potential confounding effect of medication, the results remained consistent. No reverse causation was detected.Conclusions. Our MR study reveals gut microbiome links to OA risk. Associations hold after adjusting for medication, indicating a potential causal connection between GM and OA.

Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways.

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1ß as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin-eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1ß-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

[Hyaluronic acid in the treatment of osteoarthritis: innovations in injection therapy. A review].

The review briefly presents modern understanding heterogeneity of osteoarthritis (OA) which is based on pathophysiological features of its variants. The concept of the phenotypes and endotypes of OA reflects these differences. In clinical recommendations description the emphasis on the place of hyaluronic acid is made. The mechanisms of action of sodium hyaluronate with different molecular mass are studied in detail. The results of foreign and Russian studies on efficacy and safety of different forms of hyaluronic acid are given. Personalized treatment of patients with different phenotypes of OA is shown by an example of a line of Flexotron series.

Inhibitory Effects of Reynoutria japonica Houtt. on Pain and Cartilage Breakdown in Osteoarthritis Based on Its Multifaceted Anti-Inflammatory Activity: An In Vivo and In Vitro Approach.

In the past 30 years, the number of years lived with disability due to osteoarthritis (OA) has doubled, making it an increasing global health burden. To address this issue, interventions that inhibit the progressive pathology driven by age-related low-grade inflammation, the primary mechanism of OA, are being actively pursued. Recent investigations have focused on modulating the age-related low-grade inflammatory pathology of this disease as a therapeutic target. However, no agent has successfully halted the disease's progression or reversed its irreversible course. Reynoutria japonica Houtt. (RJ), a promising East Asian herbal medicine, has been utilized for several diseases due to its potent anti-inflammatory activity. This study aims to determine RJ's capacity to inhibit OA symptoms and associated inflammation, exploring its potential for further development. In vivo and in vitro experiments demonstrated RJ's anti-OA activity and modulation of multifaceted inflammatory targets. RJ significantly inhibited pain, gait deterioration, and cartilage destruction in a monosodium iodoacetate-induced OA rat model, with its analgesic effect further confirmed in an acetic acid-induced writhing model. RJ exhibited consistent anti-inflammatory activity against multiple targets in serum and cartilage of the OA rat model and lipopolysaccharide-induced RAW 264.7 cells. The inhibition of inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinase-13, tumor necrosis factor-α, and nitric oxide synthase 2, suggests that RJ's alleviation of OA manifestations relates to its multifaceted anti-inflammatory activity. These results indicate that RJ merits further investigation as a disease-modifying drug candidate targeting OA's inflammatory pathology. To further characterize the pharmacological properties of RJ, future studies with expanded designs are warranted.

Exploring the Efficacy of Alpha-Lipoic Acid in Comorbid Osteoarthritis and Type 2 Diabetes Mellitus.

Background/Objectives. The comorbidity of osteoarthritis and type 2 diabetes mellitus poses a complex clinical challenge, complicating patient management due to overlapping pathophysiological mechanisms. This research aims to analyze the exacerbation of clinical symptoms and biochemical markers in patients with OA and T2DM compared to those with OA alone. Methods. We employed various assessment methods to evaluate inflammation, oxidative stress, and glycemic control in both cohorts. This study includes the administration of alpha-lipoic acid (ALA) to patients with comorbid OA and T2DM, monitoring its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Results. The findings indicate that T2DM significantly worsens clinical symptoms and biochemical markers in OA patients. Those with both conditions exhibited elevated indicators of inflammation and oxidative stress compared to OA-only patients. Additionally, correlations among metabolic, psychological, and inflammatory factors were identified. Body mass index emerged as a potential predictor for the deterioration of evaluated parameters. The analysis revealed that ALA administration led to statistically significant improvements in WOMAC pain scores, the Lequesne Algofunctional Index, and the AIMS-P compared to the control group. Conclusions. Further research into ALA's effects on OA progression in patients with comorbidities is essential for developing personalized treatment approaches.

A Sustained-Release Butyrate Tablet Suppresses Ex Vivo T Helper Cell Activation of Osteoarthritis Patients in a Double-Blind Placebo-Controlled Randomized Trial.

Degenerative joint disease osteoarthritis (OA) is characterized by the degeneration of cartilage, synovial inflammation and low-grade systemic inflammation in association with microbial dysbiosis and intestinal barrier defects. Butyrate is known for its anti-inflammatory and barrier protective effects and might benefit OA patients. In a double-blind placebo-controlled randomized trial, the effects of four to five weeks of oral treatment with sustained-release (SR) butyrate tablets (600 mg/day) on systemic inflammation and immune function were studied in hand OA patients. Serum markers for systemic inflammation and lipopolysaccharide (LPS) leakage were measured and ex vivo stimulation of whole blood or peripheral blood mononuclear cells (PBMCs) was performed at baseline and after treatment. Butyrate treatment did not affect the serum markers nor the cytokine release of ex vivo LPS-stimulated whole blood or PBMCs nor the phenotype of restimulated monocytes. By contrast, butyrate treatment reduced the percentage of activated T helper (Th) cells and the Th17/Treg ratio in αCD3/CD28-activated PBMCs, though cytokine release upon stimulation remained unaffected. Nevertheless, the percentage of CD4+IL9+ cells was reduced by butyrate as compared to the placebo. In both groups, the frequency of Th1, Treg, Th17, activated Th17, CD4+IFNγ+ and CD4+TNFα+ cells was reduced. This study shows a proof of principle of some immunomodulatory effects using a SR butyrate treatment in hand OA patients. The inflammatory phenotype of Th cells was reduced, as indicated by a reduced percentage of Th9 cells, activated Th cells and improved Th17/Treg balance in ex vivo αCD3/CD28-activated PBMCs. Future studies are warranted to further optimize the butyrate dose regime to ameliorate inflammation in OA patients.

Association of Tramadol Versus Codeine Prescriptions with all-cause mortality and cardiovascular diseases among patients with osteoarthritis: a systematic review and meta-analysis of propensity score-matched population-based cohort studies.

BACKGROUND: Today, the prescription of tramadol in patients with osteoarthritis (OA) has increased significantly, which can be associated with serious consequences. Contradictory results have been reported regarding the association of tramadol versus codeine with the risk of all-cause mortality (ACM) and cardiovascular diseases (CVD). METHODS: This systematic review and meta-analysis aimed to evaluate, for the first time, the association of tramadol versus codeine with the risk of ACM and CVD in OA patients for the first time. We searched PubMed, Scopus, Embase, Web of sciences, and Google Scholar with specific keywords and mesh terms to find relevant studies until January 2024. Two independent researchers did the process of searching and screening articles. Cochran's Q and I2 tests evaluated the heterogeneity of the studies. Egger's test was used to evaluate the existence of publication bias. RESULTS: Seven population-based cohort studies, matched by the propensity score method, including 1,939,293 participants, were reviewed. The study pooled results did not show a significant association between the prescriptions of tramadol versus codeine with increasing the risk of ACM in OA patients. (Hazard ratio (HR): 1.084, 95% confidence interval (95%) CI: 0.883, 1.286, P: 0.56) In addition, the prescription of tramadol versus codeine was not associated with an increased risk of CVD in OA. (HR: 1.025, 95% CI: 0.89, 1.16, P: 0.68, I2 = 37.8%) CONCLUSION: Our systematic review showed that tramadol prescription compared to codeine in OA patients was not associated with an increased risk of ACM and CVD.

Knowledge, attitude, and practice toward nonsteroidal anti-inflammatory drugs among osteoarthritis patients: a cross-sectional study.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs in patients with osteoarthritis (OA). NSAIDs are generally used at home by patients, without supervision, requiring proper knowledge and attitudes for correct practice. This study investigated the knowledge, attitude, and practice (KAP) of patients with OA toward NSAIDs. Methods This cross-sectional study enrolled patients with OA at the Qingpu Branch of Zhongshan Hospital of Fudan University between January and March 2024. The KAP scores and demographic information of respondents were collected through a self-designed questionnaire. Results There were 645 participants, with 579 (89.8%) over 45 years old and 394 (61.1%) females. The average scores for knowledge, attitude, and practice were 16.26 ± 3.79 (possible range: 0-24), 18.12 ± 1.99 (possible range: 5-35), and 29.20 ± 5.52 (possible range: 10-50), respectively. The structural equation model (SEM) found that for individuals currently using NSAIDs, the attitude had a direct effect on practice (ß = 0.978, P < 0.001). For individuals not using NSAIDs, the attitude had a direct effect on practice (ß = 0.936, P < 0.001). Conclusion This study suggested that adequate NSAID knowledge is the prerequisite for correct NSAID-related medical decisions, while attitude has a crucial intermediary effect. Healthcare professionals and society should strengthen education regarding the relevant knowledge of NSAIDs and guide the cultivation of positive attitudes toward NSAIDs.

Intra-articular corticosteroid injections for osteoarthritis: A qualitative study of patients' and clinicians' experiences.

BACKGROUND: Osteoarthritis is a leading cause of joint pain and disability. Intra-articular corticosteroid injections (IACs) are often used in primary care once other recommended treatments have failed. Evidence shows that IACs provide short-term relief of osteoarthritis symptoms, yet little is known about patients' and primary care clinicians' experiences and beliefs about their use. We explored patients' and primary care clinicians' views about IACs, including the benefits, disadvantages, perceived risks of treatment, when they are used, and factors that affect decision-making. METHODS: We conducted individual interviews with patients and primary care clinicians and used inductive thematic analysis to investigate their views and experiences of intra-articular corticosteroid injections for osteoarthritis (IACs). FINDINGS: We interviewed 38 patients and 19 primary care clinicians. We identified 6 patient themes: variation in access; awareness of IACs; views of risk and trust; effectiveness of IACs; variation in onset and effect duration; and an alternative to undesirable treatments. In the interviews with clinicians, we identified an overarching theme of caution and competence, which included eight subthemes: confidence and (dis)comfort with practical procedures; risk of adverse outcomes; training; uncertainty about evidence and guidelines; technical uncertainties; IACs use on the osteoarthritis pathway; perceived benefits and impacts of IACs; and the possibility of placebo. CONCLUSION: Patients and clinicians valued IACs' potential to relieve symptoms and improve quality of life. Variability in patients' access to treatment appears related to clinicians' confidence in delivering injections and their concerns about the evidence base. Variation in dose frequency and timing reflect clinicians' uncertainty about current guidance. Despite variation in effectiveness patients preferred IACs to other forms of pain medication and to delay or avoid surgery. IACs were mostly used as an adjunct treatment before surgery was offered. These findings can inform further research into the effectiveness of IACs and improvements in information and guidance.

Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal's potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention. METHODS: To simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC's therapeutic effects on chondrocytes. RESULTS: The results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1ß, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA. CONCLUSIONS: This study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC's comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC's therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.

Evaluation of the protective dose-dependent effect of metformin for induced osteoarthritis in rats.

Objective: To evaluate the potential protective effect of metformin against osteoarthritis development in rats. METHODS: The experimental study was conducted at the Iraqi Centre for Cancer Research and Medical Genetics, Mustansiriyah University, Baghdad, Iraq, from December 2021 to February 2022, and comprised male Sprague- Dawley mice who were divided into 5 equal groups: negative control group, osteoarthritis group subjected to monoiodoacetate induction, positive control group treated with celecoxib 30mg/kg, metformin 100mg/kg group, and metformin 200mg/kg group. Body mass index, inflammatory biomarkers, and serum C-terminal cross-linked telopeptide of type II collagen levels were noted for all the animals. Data was analysed using SPSS 24. RESULTS: Of the 35 mice, 7(20%) were in each of the 5 groups. Compared to the osteoarthritis group, metformintreated mice showed significantly reduced body mass index, inflammatory biomarker levels, and blood levels of Cterminal cross-linked telopeptide of type II collagen (p=0.05). Metformin 200mg/kg treatment had more beneficial effects than 100mg/kg dose on inflammatory biomarkers and serum C-terminal cross-linked telopeptide of type II collagen (p=0.05). CONCLUSIONS: A beneficial protective effect against the onset of osteoarthritis was produced by metformin in a dosedependent way. Additionally, metformin could lessen cartilage damage as demonstrated by a decrease in the serum levels of C-terminal cross-linked telopeptide of type II collagen in the osteoarthritis group.

Psychometric evaluation of the Adelphi Adherence Questionnaire (ADAQ©) in adults with osteoarthritis.

BACKGROUND: Medication non-adherence is a common issue in chronic illness. The World Health Organization has recognized a need for a valid and reliable method of measuring adherence to understand and mitigate non-adherence. This study aimed to psychometrically evaluate the English version of the Adelphi Adherence Questionnaire (ADAQ©), a questionnaire designed to assess patient-reported medication adherence across multiple therapy areas, in patients with Osteoarthritis (OA). METHODOLOGY: Data from the Adelphi OA Disease Specific Programme™, a survey of physicians and their consulting adult patients with OA conducted in the United States, November 2020 to March 2021, was used to assess the psychometric properties of the ADAQ. Patients completed the ADAQ, Adherence to Refills and Medication Scale (ARMS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EQ-5D-3L. The measurement model of the 13-item ADAQ was assessed and refined using latent variable modelling (Multiple Indicator Multiple Cause, confirmatory and exploratory factor analyses, item response theory, Mokken scaling, and bifactor analyses). Correlational analyses (Spearman's rank and polyserial as appropriate) with ARMS, WOMAC, and EQ-5D-3L scores assessed construct validity. Anchor- and distribution-based analyses were performed to estimate between-group clinically important differences (CID). RESULTS: Overall, 723 patients were included in this analysis (54.5% female, 69.0% aged ≥ 60). Latent variable modelling indicated a unidimensional reflective model was appropriate, with a bifactor model confirming an 11-item essentially unidimensional score. Items 12 and 13 were excluded from scoring as they measured a different concept. The ADAQ had high internal reliability with omega hierarchical and Cronbach's alpha coefficients of 0.89 and 0.97, respectively. Convergent validity was supported by moderate correlations with items of the ARMS, and physician-reported adherence and compliance. Mean differences in ADAQ score between high and low adherence groups yielded CID estimates between 0.49 and 1.05 points, with a correlation-weighted average of 0.81 points. CONCLUSION: This scoring model showed strong construct validity and internal consistency reliability when assessing medication adherence in OA. Future work should focus on confirming validity across a range of disease areas.

Patterns of pain medication usage and self-reported pain in older Irish adults with osteoarthritis: A latent class analysis of data from the Irish Longitudinal Study on Ageing.

BACKGROUND: This study aimed to identify and describe links between pain medication use and self-reported pain among people aged ≥ 50 years with osteoarthritis (OA) in an Irish population, and to examine the relationships between pain, medication usage and socioeconomic and clinical characteristics. METHODS: Secondary data analysis of wave 1 cross-sectional data from The Irish Longitudinal Study on Ageing (TILDA) was undertaken of 1042 people with self-reported doctor-diagnosed OA. We examined use of medications typically included in OA clinical guidelines, including non-opioid analgesics (e.g. paracetamol), topical and oral non-steroidal anti-inflammatory drugs (NSAIDs), opioids and nutraceuticals. Latent Class Analysis (LCA) was used to identify underlying clinical subgroups based on medication usage patterns, and self-reported pain severity. Multinomial logistic regression was used to explore sociodemographic and clinical characteristic links to latent class membership. RESULTS: A total of 358 (34.4%) of the 1042 people in this analysis were taking pain medications including oral NSAIDs (17.5%), analgesics (11.4%) and opioids (8.7%). Nutraceutical (glucosamine/chondroitin) use was reported by 8.6% and topical NSAID use reported by 1.4%. Three latent classes were identified: (1) Low medication use/no pain (n = 382, 37%), (2) low medication use/moderate pain (n = 523, 50%) and (3) moderate medication use/high pain (n = 137, 13%). Poorer self-rated health and greater sleep disturbance were associated with classes 2 and 3; depressive symptoms and female gender were associated with class 2, and retirement associated with class 3. CONCLUSIONS: Whilst pain medication use varied with pain severity, different medication types reported broadly aligned with OA guidelines. The two subgroups exhibiting higher pain levels demonstrated poorer self-rated health and greater sleep disturbance.

Can intra-articular daidzein injection reduce oxidative damage and early osteoarthritis in a rabbit temporomandibular joint model?

BACKGROUND: Oxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs. METHODS: The predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations. RESULTS: There were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007). CONCLUSIONS: An intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA.

Ononin delays the development of osteoarthritis by down-regulating MAPK and NF-κB pathways in rat models.

BACKGROUND: Osteoarthritis (OA) is featured as cartilage loss, joint pain and loss of labor, which the inflammatory reaction may play critical roles. Ononin is an isoflavone isolating from medicinal plants and has anti-inflammatory effects. Our study investigated the anti-inflammation response of ononin on OA. METHODS: Anterior cruciate ligament transection (ACLT)-induced OA operation was used to establish research model, then treated with ononin for 8 weeks. The condition of joint injury was assessed using pathological staining. The concentration of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in serum were measured by Elisa kit. The expression of collagen II and matrix metalloproteinase 13 (MMP-13) proteins to assess cartilage metabolism level by immunohistochemistry and Western blot. We detected the expression of proteins involved in the MAPK and NF-κB signaling pathways. Finally, we used molecular docking to assess the affinity of ononin for the target proteins ERK1/2, JNK1/2, p38 and p65. RESULTS: Our results confirmed that ononin ameliorated cartilage impairment through histopathological analysis by improving the morphological structures and cartilage tidal lines and decreasing Osteoarthritis Research Society International (OARSI) scores in OA rats. Moreover, ononin inhibited the secretion of above factors in OA rats. Furthermore, ononin has been shown to improve cartilage content levels in OA rats. In addition, ononin inhibited the reactivity of MAPK and NF-κB pathways in OA rats. And molecular docking indicated the ligand molecules could stably bind to the proteins of above receptors. CONCLUSION: Our results demonstrated that ononin may ameliorate cartilage damage and inflammatory response in OA rats by downgrading MAPK and NF-κB pathways, thus identifying ononin as a potential novel drug to treat OA.

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

Background: 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. Methods: 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. Results: 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-1ß, IL-6, and CRP. In patients with RA treated with adalimumab, only IL-6 and CRP correlated significantly with LCN2. Conclusions: 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.