Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage degradation, osteophyte formation, and joint dysfunction, significantly impairing the quality of life in the elderly population. Recently, RNA modifications, as a dynamic and reversible epigenetic modification, have emerged as critical players in the onset and progression of OA. This review systematically summarizes the major types of RNA modifications involved in OA, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G), and explores their roles in regulating chondrocyte autophagy, inflammatory responses, and key signaling pathways. with a primary focus on RNA methylation. Special emphasis is placed on the dynamic regulatory functions of key methyltransferases (e.g., METTL3, FTO, WTAP) and their potential contributions to OA pathogenesis. Furthermore, we address current research hotspots and controversies in the field, proposing future research directions, such as leveraging single-cell sequencing to decipher dynamic RNA modification changes during OA progression and uncovering the cooperative networks among various RNA modifications. Advancing our understanding of the biological roles and mechanisms of RNA modifications holds promise for innovative strategies in the early diagnosis, disease stratification, and targeted therapy of OA.

The growing interest in RNA-based therapeutics has positioned small interfering RNA (siRNA) as a promising tool for gene silencing with high specificity and efficacy. However, the successful clinical application of siRNA therapies requires efficient delivery systems to overcome extracellular and intracellular barriers. Chitosan, a naturally derived polysaccharide, has gained significant attention as a non-viral vector due to its biodegradability, biocompatibility, mucoadhesive properties, and capacity to enhance cellular uptake. These attributes make chitosan an attractive alternative to lipid-based nanoparticles, which currently dominate siRNA delivery platforms. Recent advancements in chitosan-based nanoformulations, including chemical modifications and functionalization strategies, have improved siRNA stability, targeting efficiency, and transfection potential, addressing key limitations such as low bioavailability and immunogenicity. Despite these advances, challenges remain in achieving optimal release kinetics, scalability, and consistent therapeutic efficacy. Future research efforts will focus on engineering chitosan derivatives with enhanced physicochemical properties, integrating multifunctional nanocarriers, and refining formulation strategies to bridge the gap between preclinical research and clinical translation. The continued development of chitosan-based siRNA therapeutics holds significant potential for advancing precision medicine and expanding treatment options for a variety of diseases, including cancer, metabolic disorders, and inflammatory conditions.

We aimed to characterize patients with hand osteoarthritis (OA) with deteriorating or improving hand pain and to investigate patients achieving good clinical outcome after four years.

We used four-year annual Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain subscale (range 0-20) measurements from the Hand OSTeoArthritis in Secondary Care cohort (patients with hand OA). Pain changes were categorized as deterioration, stable, and improvement using the Minimal Clinical Important Improvement. Good clinical outcome was categorized using the Patient Acceptable Symptom State (PASS). Associations between baseline characteristics (patient and disease characteristics, coping styles, and illness perceptions) and outcomes were investigated using multinomial or binary logistic regression, adjusted for baseline pain, age, sex, and body mass index (BMI).

A total of 356 patients (83% female, mean age 60.6 years, mean AUSCAN score 9.1) were analyzed. Pain improved for 38% of patients, deteriorated for 30% of patients, and remained stable for 32% of patients over four years. Four-year pain development followed annual trends. At baseline, 44% of patients reached PASS, and 49% of patients reached PASS at follow-up. Higher BMI, coping through comforting cognitions, and illness comprehension were positively associated with pain deterioration. Higher AUSCAN function score, mental well-being, and illness consequences were negatively associated with pain improvement. Employment (positive) and emotional representations (negative) were associated with both improvement and deterioration. Higher baseline AUSCAN function, tender joint count, and symptoms attributed to hand OA were associated negatively with PASS after four years.

The pain course of patients with hand OA is variable, not inevitably worsening, and various factors may play a role. Whether modification of these risk factors can influence pain outcomes requires further investigation.

Osteoarthritis (OA) is a highly prevalent chronic joint disorder affecting ~600 million individuals worldwide and is characterized by complex pain mechanisms that significantly impair patient quality of life. Challenges exist in accurately assessing and measuring pain in OA due to variations in pain perception among individuals and the heterogeneous nature of the disease. Conventional pain assessment methods, such as patient-reported outcome measures and clinical evaluations, often fail to fully capture the heterogeneity of pain experiences among individuals with OA. This review will summarize and evaluate current methods of pain assessment in OA and highlight future directions for standardized pain assessment. We discuss the role of animal models in enhancing our understanding of OA pain pathophysiology and highlight the necessity of translational research to advance pain assessment strategies. Key challenges explored include identifying phenotypes of pain susceptibility, integrating biomarkers into clinical practice, and adopting personalized pain management approaches through the incorporation of multi-modal data and multilevel analysis. We underscore the imperative for continued innovation in pain assessment and management to improve outcomes for patients with OA.

Knee osteoarthritis (KOA) is the leading cause of knee joint dysfunction. Manual therapy (MT) can decrease patients' levels of pain and improve their functionality. But most traditional methods focus solely on the knee joint or its surrounding tissues, neglecting the impact of the waist, hip, ankle, and lower limb alignment on KOA. The objective is to clarify the effects of the five-step knee adjustment manipulation on KOA, evaluate its efficacy, and explore new treatment approaches for manual KOA therapy.

(1) 45 healthy volunteers will be recruited to observe the differences in lower limb alignment, quadriceps cross-sectional area, knee joint range of motion (ROM), and gait between healthy individuals and KOA participants. (2) Conduct a multi-center, randomized, single-blind, controlled clinical trial. 120 eligible participants will be included and randomly assigned to a five-step knee adjustment manipulation (FS) group or a sham manipulation (SM) group with a ratio of 1:1. Each group will receive 2 sessions per week applied for 4 weeks and then be followed up for another 8 weeks. The primary outcome is visual analogue scale (VAS). The secondary outcomes include Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, ROM, quadriceps cross-sectional area (CSA), gait analysis, and so on.

This technique emphasizes a holistic approach, addressing the lumbar spine, hip, knee, and ankle joints, as well as related muscle groups, to correct lower limb alignment and restore muscle and bone balance. We think it will contribute to providing a promising alternative intervention for middle-aged and older adults with KOA.

The study was approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (Ethics No.: 2024SHL-KY-70-01). Registered in Chinese Clinical Trial Registry (No. ChiCTR2400085536).

The present study aimed to compare the efficacy and safety of loxoprofen sodium cataplasm (LSC) with those of flurbiprofen cataplasm (FPC) in osteoarthritis (OA) treatment. In this multicenter, randomized controlled trial, subjects meeting the inclusion and exclusion criteria were randomly assigned to the two treatment groups. According to the manufacturer's instructions, the first group received LSC once daily, with the application of one patch per area for 2 weeks, whereas the second group received FPC twice daily, with the application of one patch per area for 2 weeks. The treatment response was evaluated based on the Visual Analog Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, Lysholm score and adverse events for 296 patients enrolled across three subcenters, with 192 patients in the LSC group and 104 patients in the FPC group. The treatment effectiveness rates, based on the VAS, WOMAC global and Lysholm scores, were 74.46, 61.41 and 85.25%, respectively, for the LSC group and 43.14, 31.37 and 66.67%, respectively, for the FPC group. Regardless of the effectiveness criterion used, the LSC group exhibited a superior treatment effectiveness rate compared with the FPC group. After 2 weeks of treatment, OA symptoms improved in both groups, with the LSC group exhibiting lower VAS (P<0.05) and WOMAC global scores (comprising pain, stiffness and physical function scores) compared with the FPC group (P<0.05), while the Lysholm score was higher in the LSC group compared with the FPC group (P<0.05). The FPC group experienced more general adverse events (P>0.05) and dressing shedding (P<0.05) compared with the LSC group, whereas the LSC group had more specific adverse events (such as skin itching, fever and allergy) compared with the FPC group (P>0.05). The results suggested that compared with FPC, LSC exhibited higher short-term efficacy and a consistent safety profile. The present study was registered at Chinese Clinical Trial Register (chictr.org.cn; ChiCTR2300072504; date of registration, June 15, 2023).

Links between cathepsin K and the pathophysiology of osteoarthritis (OA) can be established, not least because of the overabundance of cathepsin K in the serum of OA patients and the upregulation of cathepsin K in degraded cartilage in animal models of OA. Chondrocytes, chondroclasts, or osteoclasts contribute to the accumulated cathepsin K at the diseased osteochondral junction. After a general presentation of OA and cartilage physiology, as well as its degradation processes, we describe the function of cathepsin K and its effect on cartilage degradation via type II collagen cleavage. An overview of the most promising cathepsin K inhibitors is then presented, together with their in vitro effects. Although intensive research on cathepsin K inhibitors initially focused on bone resorption, there is growing interest in the potential of these drugs to prevent cartilage degradation. In this review, we summarize the pre-clinical and clinical trials that support the use of cathepsin K inhibitors in the treatment of OA. To date, no molecules of this type are commercially available, although a few have undergone clinical trials, but we believe that the development of cathepsin K inhibitors could broaden the therapeutic arsenal for the treatment of OA.

Total knee arthroplasty (TKA) is an established surgical procedure for severe knee osteoarthritis (KOA) that has provided excellent outcomes. While several studies have reported that patients with preoperative central sensitization (CS) experienced worse pre- and post-operative pain and outcomes, the evidence is limited. We conducted this study to determine the impact of CS on perioperative knee pain in TKA for severe KOA.

A retrospective cohort study of 66 patients who underwent bilateral TKA for bilateral severe KOA was conducted. Multiple linear regression models that included covariates and scaled estimated regression coefficients were used to examine the impact of CS on the patients' pre- and post-operative pain subscale values on the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the improvement of KOOS pain. Postoperative KOOS pain was assessed at 3 months postoperatively, while other evaluation items including preoperative KOOS pain, CS, and pain self-efficacy were assessed on admission.

CS had a negative impact on pre- and post-operative KOOS pain (preoperative, β: -0.28, 95% confidence interval [CI] -18.53, -0.92; postoperative, β: -0.26, 95%CI -14.09, -0.44; p < 0.05). High pain self-efficacy had a positive impact on preoperative KOOS pain (β: 0.25, 95%CI 0.32, 18.08; p < 0.05). However, CS did not influence the improvement of KOOS pain.

These results demonstrate that CS had a negative impact on pre- and post-TKA knee pain in patients but did not affect the improvement of knee pain. TKA provides sufficient pain relief for severe KOA, with or without CS. Further research is required to improve pre- and post-operative knee pain in KOA patients with CS.

To analyze the effects of exergames on rehabilitation outcomes in osteoarthritis (OA) patients.

A systematic review was reported according to the PRISMA statement. Randomized controlled trials (RCTs) were searched in Pubmed, Scopus, WoS, CINAHL, and PEDro (inception to November 2023). Studies that applied non-immersive exergames and assessed physical, functional, cognitive, pain, and psychosocial outcomes were included. Comparisons were other exercise modalities and non-intervention. Methodological quality was assessed with PEDro scale, and risk of bias (RoB) was assessed with Cochrane RoB-2 tool.

Eight studies were included (total of participants = 401). The mean PEDro score was 6.1, and seven studies had high RoB. Seven studies involved knee OA and one cervical OA. The most frequent duration for interventions was four weeks. Exergames were more effective than controls in at least one outcome in all studies. The outcomes for which exergames were most effective were functional disability, postural balance, muscle strength, proprioception, gait, range of motion, pain, quality of life, depression, and kinesiophobia.

Non-immersive exergames constitute an effective strategy for optimizing several relevant outcomes in rehabilitation. However, more RCTs with high methodological quality are required to deepen the knowledge about the multidimensional effects of exergames in OA patients.

Osteoarthritis (OA) is a chronic condition in which pain significantly affects quality of life, often leading to reduced physical activity and disability. Globally, an estimated 595 million people are affected, with the numbers likely to increase owing to an aging population and rising obesity rates. Effective pain management is crucial, yet current treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, often provide limited relief and come with risks. One reason for this limited success is the insufficient recognition of the importance of psychosocial factors and heterogeneity of patients with OA (such as anxiety and depression), which can exacerbate pain and its impacts. The variability in patient pain experiences highlights the potential value of pain phenotyping, which involves a comprehensive assessment of pain characteristics to tailor treatments to individual needs. Antidepressants, particularly serotonin-norepinephrine reuptake inhibitors (SNRIs), show promise in alleviating both psychological symptoms and OA-related pain, but their effectiveness varies among individuals. Therefore, further research into standardized pain phenotyping methods and their integration into antidepressant treatment is needed to improve efficacy and minimize side effects through more personalized approaches.

Temporomandibular joint (TMJ) osteoarthritis with pain is a highly prevalent disorder affecting patients' quality of life. A comprehensive understanding of cell type diversity and its dynamics in painful TMJ osteoarthritis (TMJOA) is lacking. Here, we utilized an inflammatory TMJOA mouse model via intra-articular injection of CFA. TMJOA mice exhibited cartilage remodeling, bone loss, synovitis, increased osteoarthritis (OA) score, and orofacial pain, recapitulating hallmark symptoms in patients. Single-cell transcriptomic profiling of the TMJ was performed in conjunction with mouse genetic labeling, tissue clearing, light sheet and confocal 3D imaging, multiplex RNAscope, and immunodetection. We visualized, reconstructed, and analyzed the distribution and density of nociceptive innervation of TMJ at single-axon levels. We systematically mapped the heterogeneity and anatomical position of blood endothelial cells, synovial fibroblasts, and immune cells, including Cx3cr1-positive barrier macrophages. Importantly, TMJOA mice exhibited enhanced neurovascular coupling, sublining fibroblast hyperplasia, inflammatory immune cell expansion, disrupted signaling-dependent cell-cell interaction, and a breakdown of the sandwich-like organization consisting of synovial barrier macrophages and fibroblasts. By utilizing a mouse model with combined TMJ pain history and OA, we reveal the cellular diversity, anatomical structure, and cell dynamics of the TMJ at single-cell resolution, which facilitate our understanding and potential targeting of TMJOA.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by the destruction of joint cartilage and synovitis, affects over 7 % of people worldwide. Disease-modifying treatments for OA still face significant challenges. Chondrocytes, as the exclusive cellular component of articular cartilage, play a pivotal role in synthesizing the intricate matrix of cartilage, thereby assuming a critical responsibility in facilitating its renewal and repair processes. However, oxidative stress within chondrocytes and subsequent apoptotic cell death plays significant roles in the progression of OA. Therefore, targeting apoptosis inhibition and mitigation of oxidative stress in chondrocytes represents a promising therapeutic strategy for OA. This study develops a type II collagen-targeting peptide (WYRGRLC) modified bilirubin/rapamycin carrier-free nanoparticle (PP/BRRP) and evaluate its therapeutic potential for OA. The PP/BRRP system exhibits remarkable chondrocyte-targeting ability, enabling the rupture of highly oxidized chondrocytes and subsequent release of bilirubin and rapamycin. This dual payload effectively scavenges reactive oxygen species, triggers autophagy, and suppresses the mTOR pathway, thereby augmenting anti-inflammatory and anti-apoptotic effects. The in vivo experiments further validate the retention and therapeutic efficacy of PP/BRRP in rat joints affected by OA. Overall, PP/BRRP exhibits significant potential for intervention and treatment of OA.

Musculoskeletal pain has a high prevalence of transition to chronic pain and/or persistence as chronic pain for years or even a lifetime. Possible mechanisms for the development of such pain states are often reflected in inflammatory or neuropathic processes involving, among others, cytokines and other molecules. Since biologics such as blockers of TNF or IL-6 can attenuate inflammation and pain in a subset of patients with rheumatoid arthritis, the question arises to what extent cytokines are involved in the generation of pain in human musculoskeletal diseases. In numerous experimental non-human studies, cytokines have been shown to alter neuronal sensitivity in the peripheral and central nociceptive systems. In this review, we addressed the involvement of cytokines in postoperative pain, complex regional pain syndrome, rheumatoid arthritis, osteoarthritis, temporomandibular joint disease, low back pain and fibromyalgia using PubMed searches including meta-analyses of data. There is evidence that certain pro- and anti-inflammatory cytokines are regulated in all of these diseases, often in both acute and chronic disease states. However, within these data, we found a great deal of heterogeneity in the association between cytokine levels and pain. Neutralization of cytokines showed antinociceptive effects in subgroups of patients with chronic pain (e.g., in a proportion of patients with rheumatoid arthritis), but failed to reduce chronic pain in other diseases (e.g., osteoarthritis). More systematic studies are needed to unravel the pathogenic role of cytokines in human musculoskeletal pain, taking into account the disease process and the mechanisms of pain initiation and maintenance.

Considerable research has shown the benefits of transcranial direct current stimulation (tDCS) for the alleviation of pain associated with knee osteoarthritis (KOA). Still, a large variance in study protocols and observations across publications exists. We here thus completed a systematic review and meta-analysis to comprehensively and quantitatively characterize the effects of tDCS on KOA-related pain. A search strategy based on the Population, Intervention, Comparison, Outcome, and Study design (PICOS) principle was used to obtain the publications in 7 databases. Studies exploring the effects of tDCS on KOA-related pain were screened, and eligible studies were included. Ten studies of 518 participants using Visual Analogue Scale or Numeric Rating Scale to assess pain were included in the systematic review, and 9 of them were included in meta-analysis. The quality of these studies was good. Compared to control, tDCS induced significant short-term improvements in KOA-related pain with medium heterogeneity (standardized mean difference [SMD] = -0.91, 95% confidence interval [-1.24, -0.58], P < 0.001, I2 = 61%). Subgroup analyses showed that both home-based (SMD = -1.32, 95% CI [-1.65, -0.99], P < 0.001, I 2 = 0%) and laboratory-based intervention (SMD = -0.66, 95% CI [-0.99, -0.33], P < 0.001, I 2 = 40%) with at least 5 sessions per week (SMD = -1.02, 95% CI [-1.41, -0.64], P < 0.001, I 2 = 65%) and/or with a total number of at least 10 sessions (SMD = -1.12, 95% CI [-1.51, -0.74], P < 0.001, I 2 = 59%) can induce maximum benefits for the alleviation of KOA-related pain. The results here showed that tDCS is of great promise to alleviate KOA-related pain. Still, future studies with more rigorous design are needed to confirm the observations from this work, which can ultimately help the determination of appropriate intervention protocol that can maximize such benefits.

The effectiveness and practicality of blood flow restriction training (BFRT) as a nonsurgical intervention for treating patients with knee injuries are uncertain because of the small size of BFRT trials and inconsistent results.

To conduct a meta-analysis comparing the effectiveness of BFRT versus traditional resistance training in patients with knee osteoarthritis (OA) in terms of pain, muscle strength, functional performance, self-reported function, muscle size, and adverse events during exercise.

Systematic review; Level of evidence: 1.

Under the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the Web of Science, PubMed, EMBASE, and other databases for randomized controlled trials of BFRT interventions in patients with knee OA. Methodological and quality evaluations, heterogeneity analysis, and subgroup analysis of the included studies were conducted, and effect sizes were evaluated using mean differences or standardized mean differences (SMDs). Subgroup and sensitivity analyses were used to explore the sources of heterogeneity.

Of 2826 initial studies, 6 studies (N = 228 patients) were included. The results of the meta-analysis indicated that compared with resistance training, BFRT did not significantly affect pain relief (SMD, -0.02 [95% CI, -0.30 to 0.26]; P = .88), muscle strength (SMD, 0.32 [95% CI, -0.33 to 0.96]; P = .33), functional performance (SMD, 0.25 [95% CI, -0.29 to 0.80]; P = .36), or self-reported function (SMD, -0.252 [95% CI, -0.88 to 0.45]; P = .52). However, BFRT reduced the risk of adverse events (risk ratio, 0.45 [95% CI, 0.20 to 1.01]; P = .05). Subgroup analysis revealed that compared with low-load resistance training, BFRT significantly increased muscle size (SMD, 0.88 [95% CI, 0.09 to 1.68]; P = .02). The quality-of-evidence assessment indicated that the evidence level for the above outcomes was low and that the strength of the recommendation was weak.

The results of our meta-analysis indicated that compared with resistance training, BFRT did not significantly improve symptom outcomes in patients with knee OA. It is important to acknowledge that the findings were limited by the small number of studies and sample sizes that were included.

Neuropathic pain (NP) represents a debilitating and refractory condition. However, the understanding of NP and the current treatment approaches available for its management are limited. Therefore, there is a significant need to address the dearth of effective therapeutic interventions. This study aims to investigate the regulation of transient receptor potential vanilloid 1 (TRPV1) and cyclin-dependent kinase 5 (CDK5) expression levels by miR-142-5p as a common upstream molecule, and to delve into the mature process of miR-142-5p from the perspective of N6-methyladenosine (m6A) modification.

To assess the RNA levels of TRPV1, CDK5, miR-142-5p, pre-miR-142, and pri-miR-142, quantitative PCR with reverse transcription (RT-qPCR) was utilized. Western blot analysis was employed to determine changes in protein expression for TRPV1 and CDK5. For assessing the interaction mechanism and binding site between TRPV1 and CDK5, various techniques were applied, including mass spectrometry, coimmunoprecipitation (co-IP), and glutathione-S-transferase (GST)-pulldown assays. The subcellular localization of TRPV1 on the cell membrane was visualized through immunofluorescence, and the translocation was confirmed by western blot analysis after performing membrane-plasma separation in parallel. Moreover, intracellular calcium transport was monitored using calcium imaging as an indicator of cell excitability. The binding of miRNA-142-5p to the 3'UTR of TRPV1 and CDK5 was investigated using the dual-luciferase reporter assay. The overall level of m6A was first determined by RNA m6A methylation assay, and subsequently the methylation level of pri-miR-142 was assessed using the meRIP assay to detect m6A modification. In addition, an in vivo rat chronic constriction injury (CCI) model was established, and miR-142-5p agomir or antagomir was injected intrathecally. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IL-6 and TNF. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were examined.

The expression levels of TRPV1 and CDK5 were found to be upregulated not only in the in vivo CCI model but also in the in vitro lipopolysaccharide (LPS) treatment cell model as well. CDK5 was observed to phosphorylate TRPV1 at T406, prompting the translocation of TRPV1 to the cell membrane and consequent augmentation of cellular excitability. Notably, CDK5 was found to directly bind to TRPV1, and the binding region was localized within the 1-390 amino acid sequence of TRPV1. According to database predictions, miR-142-5p, identified as a shared upstream molecule of TRPV1 and CDK5, exhibited downregulation following induction by NP. MiR-142-5p was shown to simultaneously bind to the mRNA of CDK5 and TRPV1, thereby inhibiting their expression. After LPS treatment, it was observed that pri-miR-142 expression increased, while pre-miR-142 and miR-142-5p expression decreased, suggesting inhibition of the maturation process of pri-miR-142. In addition, the overall level of m6A and in particular the pri-miR-142 m6A modification increased upon LPS treatment. Knockdown of METTL14 led to decreased pri-miR-124 expression, increased pre-miR-124 expression, and enhanced mature miR-142-5p expression, indicating the relief of miR-142-5p maturation repression. The in vivo results indicated that miR-142-5p negatively regulated the expression of CDK5 and TRPV1, suppressed the expression of inflammatory factors IL-6 and TNF, and improved the PWMT and PWTL.

In this study, we perform a thorough investigation to examine the effects of CDK5 and TRPV1 on NP, elucidating their binding relationship and the impact of CDK5 on the membrane transport of TRPV1. Notably, our findings reveal that miR-142-5p, acting as a crucial upstream molecule, exhibits inhibitory effects on the expression of both CDK5 and TRPV1. Moreover, we observe that METTL14 facilitates the m6A modification of pri-miR-142, thereby impeding the maturation transition of pri-miR-142 and ultimately leading to the downregulation of mature miR-142-5p.

Ethylene oxide (EO) is widely used as a disinfectant and is also a common environmental pollutant. Exposure to EO has been associated with various systemic diseases, posing crucial health risks. However, EO is frequently employed as a sterilizing agent in orthopedics, while its association with the risk of skeletal system diseases remains insufficiently evaluated. This study aims to investigate the association between EO exposure and the risk of Osteoarthritis (OA), a prevalent orthopedic condition.

A total of 3,386 participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 and 2017-2018 cycles, including 952 individuals with OA. Box plots assessed EO concentration differences between OA and non-OA groups. Weighted logistic regression models and restricted cubic spline (RCS) models were used to evaluate the relationship between EO exposure and OA risk. Subgroup analysis and interaction test explored variations in the association across different characteristics.

No significant difference in EO concentrations was found between OA and non-OA groups. In multivariate logistic regression, high EO level exposure was significantly associated with increased OA risk. Additionally, a nonlinear U-shaped and J-shaped association was observed in the unadjusted and adjusted RCS models, respectively. Subgroup analysis revealed that the association between EO exposure and OA risk was more pronounced in the 20-40 and 40-65 age groups, never smokers (Not at all), and those with low calcium levels (< 8.5 mg/dL) or low vitamin D levels (< 75 nmol/L).

EO exposure is associated with OA risk, exhibiting a J-shaped relationship, with this association being particularly pronounced in individuals under 65 years old or those with low calcium or vitamin D levels. Further prospective studies are needed to examine the association between EO exposure and OA risk.

Osteoarthritis (OA) represents a condition under the influence of central nervous system (CNS) regulatory mechanisms. This investigation aims to examine the causal association between viral infections of the central nervous system (VICNS) and inflammatory diseases of the central nervous system (IDCNS) and knee osteoarthritis (KOA) at the genetic level.

In this investigation, VICNS and IDCNS were considered as primary exposure variables, while KOA served as the primary outcome. Employing a two-sample mendelian randomization (MR) approach, we conducted an analysis utilizing summary data derived from genome-wide association studies (GWAS). The GWAS summary data pertaining to VICNS and IDCNS were procured from the Finnish consortium, whereas the IEU OpenGWAS database furnished the requisite data for KOA. To ensure the robustness of our genetic causal assessment, a comprehensive array of sensitivity analyses was undertaken, encompassing evaluations of heterogeneity, horizontal pleiotropy, outlier identification, leave-one-out analyses, and assessment of the normal distribution.

The results of the MR analyses revealed a suggestive positive genetic causal relationship between VICNS and KOA (P = 0.012, odds ratio [OR] with a 95% confidence interval [CI] of 1.033 [1.007-1.059]). Conversely, the MR analyses did not indicate any evidence of genetic causation between IDCNS and KOA (P = 0.575, OR 95% CI = 0.986 [0.940-1.035]). Importantly, the genetic causal assessment of the exposure and outcome variables did not demonstrate any indications of heterogeneity, horizontal pleiotropy, or outliers. Furthermore, this assessment remained robust against the influence of individual single nucleotide polymorphisms (SNPs) and exhibited adherence to a normal distribution.

The result of this study has elucidated a suggestive positive genetic causal link between the VICNS and KOA. However, no such genetic causal relationship was observed between the IDCNS and KOA. These findings substantiate the genetic underpinnings supporting the association between the CNS and OA.

Our understanding of osteoarthritis (OA) has evolved from a degenerative disease to one in which low-grade, chronic inflammation plays a central role. In addition, evidence suggests that OA is accompanied by both peripheral and central nervous system sensitization that can cause pain. It has been demonstrated that transcutaneous vagus nerve stimulation (tVNS) can relieve pain, inflammation, and central sensitization in other conditions including fibromyalgia, pelvic pain, and headaches. We aimed to assess the efficacy and safety of tVNS on nociceptive pain, central sensitization, and physical function in knee OA.

In this 12-week study, we stimulated the auricular branch of the vagus nerve with an auricular electrode connected to a transcutaneous electrical nerve stimulation device once a day for 3 days each week for 12 weeks. A total of 68 patients with chronic knee OA were randomly assigned to the active and sham groups (34 patients in each group). We used a variety of outcome measures, including the visual analog scale (VAS), pressure pain threshold (PPT), knee injury and osteoarthritis outcome score (KOOS), PainDETECT (PD-Q) and Douleur Neuropathique 4 (DN4) questionnaires. Outcome measures were recorded at baseline, At the end of the stimulation period, and then after 4 weeks.

In the active group, compared to baseline, there was a significant improvement in VAS scores between the first and second follow-up visits (P < 0.001). A significant improvement in PPT was seen in the right knee, left knee, and right elbow in active tVNS, and this improvement persisted for four weeks post-intervention. Meanwhile, in the sham group, right knee PPT was improved but not maintained. There were statistically significant improvements in the PD-Q and DN4 scores in the active tVNS group (P < 0.001), whereas in the sham group, DN4 questionnaire did not show any improvement. In terms of functional outcomes, the improvement in KOOS was significant only in the active group (31.44 ± 18.49, P < 0.001). No serious adverse events were observed.

There is preliminary evidence to support the benefits of tVNS in OA, suggesting that neuromodulation can be used as an adjunct to existing pharmacological and non-pharmacological treatments.

The study was registered on ClinicalTrials.gov (NCT05387135) on 24/05/2022.

Osteoarthritis (OA) is a common chronic musculoskeletal disease with heterogeneous clinical manifestations and variable responses to different treatments. Unfortunately, there is no effective disease modifying therapy at present that can alter the natural course of the disease. Cell therapy based on mesenchymal stromal cells (MSCs) may offer an attractive therapeutic option for OA with their multiple modes of action, particularly immune-regulatory and regenerative capacities.

In this narrative review, updates on mode of action based on patient's data, factors that can influence the efficacy of MSC treatment, current status in clinical application of MSCs as seen from randomized, controlled OA trials are introduced as well as the author's perspectives in the future of MSCs as OA therapeutics.

Symptomatic relief is not sufficient to justify the high cost associated with culture-expanded stem cells. Its advantages and efficacy over simple and low risk/cost modalities should be seriously reevaluated. Also, as the short-term strategy, efforts should be made to lower the cost of MSC therapy. In the future, multiomics technology may help to predict that subgroup of patients who will favorably respond to stem cell treatment, which would enhance the cost effectiveness and therapeutic benefit of MSC therapy.

Osteoarthritis (OA) is the most common degenerative joint disease affecting millions of people worldwide. Garlic-derived exosomes (GDEs) are nanoparticles extracted from garlic that exhibit anti-inflammatory effects on other diseases, but the effect of GDEs on OA has not been elucidated. In this study, GDEs were extracted and characterized. Chondrocytes were treated with IL-1β and incubated with GDEs in vitro, and the expression of cartilage matrix components (collagen II and aggrecan) and matrix degrading enzymes (MMP3 and MMP9) was evaluated via Western blotting. Changes in the MAPK pathway was also examined using Western blotting. The transcriptomic changes associated with GDE intervention were evaluated using high-throughput RNA-seq method. In vivo, we used anterior cruciate ligament transection (ACLT) combined with destabilization of the medial meniscus (DMM) surgery to establish a mouse OA model, and GDEs was intraarticularly injected into the joint cavity. The therapeutic effect of GDE was evaluated by behavioral and histopathological analysis. The results showed that IL-1β treatment inhibited the expression of collagen II and aggrecan, and upregulated the expression of MMP3 and MMP9, while GDE intervention alleviated these effects. GDEs also inhibited the phosphorylation of ERK, JNK, and P38. In vivo, GDE alleviated the sensitivity to heat stimulation and altered walking gait in a mouse OA model. Histopathological analysis indicated that GDE intervention ameliorated joint destruction in the knee joint without obvious toxicity. The results proved that GDEs alleviated the progression of OA in vitro and in vivo, and may be a potential disease-modifying drug for OA.

High-intensity interval training (HIIT) is considered an effective therapy strategy for improving chronic pain associated with osteoarthritis (OA). Perineuronal nets (PNNs) are specialized extracellular matrix structures in the cerebral cortex that play a crucial role in regulating chronic pain. However, little is unknown whether HIIT could alleviate OA pain sensitization by reducing PNN levels. This study aimed to determine whether HIIT could reduce sensitivity of the affected joint(s) to pain in a chronic pain model in rats with OA. A rat model of interest was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Thereafter, the mechanical withdrawal thresholds (MWTs) and PNN levels in the contralateral medial prefrontal cortex (mPFC) were measured in rats in the presence or absence of HIIT alone or in combination with injection of chondroitinase-ABC (ChABC) into the contralateral mPFC (inducing the degradation of PNNs), respectively. Results indicated that rats with OA exhibited significant reductions in MWTs, but a significant increase in the PNN levels; that HIIT reversed changes in MWTs and PNN levels in rats with OA, and that pretreatment of ChABC abolished effects of HIIT on MWTs, with PNN levels not changed. We concluded that pain sensitization in rats with OA may correlate with an increase in PNN levels in the mPFC, and that HIIT may increases OA pain-sensitive threshold by reduction of the PNN levels in the mPFC. Keywords: Osteoarthritis, Chronic pain, Pain sensitization, High-intensity interval training, Perineuronal nets.

This study aimed to investigate the relationship between clinical findings and the trabecular microstructure of the subchondral bone in patients with hip osteoarthritis (OA) due to developmental dysplasia of the hip (DDH) using multidetector row computed tomography (MDCT).

A total of 63 patients (69 hips) with OA due to DDH were retrospectively reviewed, with 12 healthy controls being included for comparison. Clinical evaluation was performed using the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ). The trabecular bone microstructure was analyzed using MDCT. Regions of interest in the subchondral trabecular bones of the acetabulum and femoral head were defined in the coronal view, and various trabecular microstructural parameters were evaluated.

Bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) exhibited a significant positive correlation with the OA stage, whereas trabecular separation (Tb.Sp) showed a negative correlation. In addition, BV/TV and Tb.Th were negatively correlated with the JHEQ total and pain scores, whereas Tb.Sp was positively correlated with the pain score in all regions.

This is the first study to evaluate the bone microstructure and its relationship with clinical findings in patients with hip OA due to DDH. Our findings suggest that as OA progresses, osteosclerotic changes increase in the acetabulum and femoral head; these changes are associated with worsening clinical symptoms, particularly pain. Targeting the subchondral bone may emerge as a novel treatment strategy for patients with OA due to DDH; nevertheless, further comprehensive studies are required.

Resistance training (RT) is recognized in clinical guidelines as a beneficial treatment for knee osteoarthritis (KOA), but the efficacy of different RT types is not well-established.

This network meta-analysis (NMA) aimed to compare the effects of different types of RT, namely, isometric muscle strengthening (IMMS), isokinetic muscle strengthening (IKMS) and isotonic muscle strengthening (ITMS), on pain, function and quadriceps muscle strength of patients with KOA.

A systematic search was conducted up to September 2023 on databases, including PubMed, Cochrane Library, EMbase, Web of Science and China National Knowledge Infrastructure. The included studies comprised randomised controlled trials (RCTs) comparing RT with conventional rehabilitation and physiotherapy or other types of RT.

Compared with the control group (CG) that received conventional physiotherapy, IKMS was optimal in terms of pain relief (MD = -1.33, 95% CI: -1.83 to -0.83), function (MD = -12.24, 95% CI: -17.29 to -7.19) and knee extension torque (SMD = -0.44, 95% CI: -0.74 to -0.14).

Compared with conventional rehabilitation therapy, all three types of RT can improve pain and knee-joint function in KOA patients. IKMS demonstrated the best results among the different RT modalities.

PROSPERO registration number: CRD42023448579.

The aims of this review were to identify and to analyze the clinical studies that used subcutaneous injections of dextrose for treating musculoskeletal pain, in order to establish an overview.

A systematic search was carried out in scientific databases including Web of Science, Cochrane Central Register of Controlled Trials, PUBMED and other sources, up until March 2024. We included clinical studies that used subcutaneous injections of dextrose in the treatment of individuals with musculoskeletal pain associated with tendinopathies, enthesopathy, osteoarthritis, ligament sprains, muscle strains or bursitis of various locations.

Twenty studies that met the criteria were included in this review; of those, 13 were randomized clinical trials, one non-randomized comparative study and six were case series studies, comprising a total of 1226 patients. In all included studies, efficacy in pain reduction was reported in the groups treated with dextrose when comparing evaluations at baseline, short term and medium term.

Subcutaneous injections of dextrose could be a beneficial treatment for reducing musculoskeletal pain; however, factors such as the high heterogeneity in the treatment schemes, uncertainty in the mechanisms of action and the level of evidence found, indicate that this technique is still under development.

Osteoarthritis (OA) is a common chronic degenerative joint disease and a major contributor to disability and elevated morbidity rates worldwide. This study assesses the epidemiological trends of OA from 1990 to 2021, analyzing data by sex, affected joint sites, and Socio-Demographic Index (SDI) across global, regional, and national levels.

Data on OA were obtained from the (Global Burden of Disease Study) 2021. The age-standardized rates (ASR) for OA were computed, and the estimated annual percentage changes (EAPC) in ASR were determined to evaluate trends in incidence and disability-adjusted life years (DALYs) over the past three decades. Pearson's correlation analysis was conducted to explore the relationship between ASR and the Socio-Demographic Index (SDI). Additionally, Joinpoint regression software and age-period-cohort (APC) analysis were applied for a comprehensive examination of the OA data.

From 1990 to 2021, the global burden of OA has markedly increased. In 2021, there were approximately 466.3 million new OA cases, with an ASR of incidence (ASIR) of around 535 per 100,000 population. The prevalence of OA reached about 606.9 million cases, and DALYs rose to approximately 213 million. The burden of OA is significantly higher in women compared to men, as reflected by higher ASR of incidence, prevalence, and DALYs associated with OA. In 2021, the ASR of incidence was positively associated with the SDI regions. Globally, knee osteoarthritis (KOA) remains the most common form of OA. Among the various risk factors, high body mass index (BMI) emerged as the most critical contributor to OA.

From 1990 to 2021, the global burden of OA has steadily increased, leading to a significant decline in health and overall quality of life. The global prevalence of OA indicates higher incidence rates among women and in countries with a higher SDI. Governments and policy makers globally must prioritize increasing awareness of the risk factors and consequences related to OA, promote early diagnostic and therapeutic services, and implement targeted interventions to mitigate the growing burden of OA.

The effective regeneration of bone/cartilage defects remains a significant clinical challenge, causing irreversible damage to millions annually.Conventional therapies such as autologous or artificial bone grafting often yield unsatisfactory outcomes, emphasizing the urgent need for innovative treatment methods. Biomaterial-based strategies, including hydrogels and active scaffolds, have shown potential in promoting bone/cartilage regeneration. Among them, injectable hydrogels have garnered substantial attention in recent years on account of their minimal invasiveness, shape adaptation, and controlled spatiotemporal release. This review systematically discusses the synthesis of injectable hydrogels, bioinspired approaches-covering microenvironment, structural, compositional, and bioactive component-inspired strategies-and their applications in various bone/cartilage disease models, highlighting bone/cartilage regeneration from an innovative perspective of bioinspired design. Taken together, bioinspired injectable hydrogels offer promising and feasible solutions for promoting bone/cartilage regeneration, ultimately laying the foundations for clinical applications. Furthermore, insights into further prospective directions for AI in injectable hydrogels screening and organoid construction are provided.

Background Knee osteoarthritis (KOA) is characterized by cartilage degradation, osteophyte formation, and synovitis. Cartilage degradation in KOA begins with the loss of aggrecan, primarily due to A Disintegrin and Metalloproteinase with Thrombospondin Motif 5 (ADAMTS5), which is produced by chondrocytes and synovial cells and a key target for therapeutic intervention. Current treatments for KOA primarily focus on pain relief, as disease-modifying osteoarthritis drugs (DMOADs) remain unavailable. Electroacupuncture (EA), applying electrical stimulation to acupoints, has been investigated for its potential to alleviate KOA symptoms; however, the specific effects of different acupoint combinations remain unclear. This study investigates the effect of EA on pain and cartilage degeneration in a KOA rat model by examining ADAMTS5 expression in synovial tissue. Materials and methods Male Wistar rats were divided into five groups: control, sham-operated, KOA model, KOA treated with EA at ST36 (Zusanli)-LR8 (Ququan) (KOA+LR8), and KOA treated at ST36-Ex-LE2 (Heding) (KOA+Ex-LE2). The DMM (destabilization of the medial meniscus) procedure induced KOA, and EA was applied thrice weekly for four weeks. The rotarod test was used to assess motor coordination, and samples were collected for immunofluorescence, Western blot, and histological analysis. Pain was assessed via c-fos expression in the spinal cord, while Safranin O-Fast Green staining was used to evaluate cartilage degeneration via the Osteoarthritis Research Society International (OARSI) scoring system. Results The KOA group post-surgery showed reduced motor coordination, while EA at both ST36-LR8 and ST36-Ex-LE2 enhanced performance (day 28: control: 28.8 ± 0.6, sham: 28.4 ± 3.7, KOA: 19.7 ± 0.9, KOA+LR8: 24.8 ± 1.5, KOA+Ex-LE2: 26.9 ± 1.2). Expression of c-fos, elevated in the KOA group, was significantly suppressed by EA (control: 7.6 ± 0.9, sham: 13.6 ± 2.8, KOA: 24.5 ± 2.1, KOA+LR8: 12.8 ± 0.9, KOA+Ex-LE2: 17.0 ± 1.2). Histologically, KOA rats showed severe cartilage degradation and osteophyte formation, while EA at ST36-Ex-LE2 significantly reduced these changes (control: 0.2 ± 0.1, sham: 0.4 ± 0.2, KOA: 1.8 ± 0.4, KOA+LR8: 1.0 ± 0.2, KOA+Ex-LE2: 0.5 ± 0.2). The ST36-LR8 group also showed improvements, although less pronounced than the ST36-Ex-LE2 group. Western blotting revealed that DMM-induced ADAMTS5 expression was significantly inhibited by EA at ST36-Ex-LE2 but not at ST36-LR8 (control: 1.0 ± 0, sham: 1.2 ± 0.4, KOA: 3.0 ± 0.3, KOA+LR8: 2.1 ± 0.3, KOA+Ex-LE2: 1.4 ± 0.4). Conclusion EA at ST36-Ex-LE2 showed a remarkable protective effect on articular cartilage by inhibiting ADAMTS5 expression from synovium, suggesting that it can break the vicious cycle of synovitis and cartilage destruction. In contrast, EA at ST36-LR8 had a moderate effect on cartilage degeneration and ADAMTS5 expression. The difference in efficacy may be due to the anatomical differences between acupoints. ST36-Ex-LE2 coincides with an area rich in synovial fibroblasts and mast cells involved in inflammation and pain. This highlights the importance of acupoint selection to maximize the therapeutic effect of EA. The specificity of this acupoint combination provides a potential strategy for managing KOA and slowing the progression of the disease. Further studies are needed to elucidate the detailed mechanisms behind the effects of EA and explore its potential as an alternative or complementary treatment for KOA.

Background/Objectives: The Star Excursion Balance Test (SEBT) is a simple and feasible tool for assessing dynamic balance in individuals with knee osteoarthritis (KOA). It has an advantage as it replicates dynamic balance better than other static balance tools. This study aims to determine how reliable SEBT is among people with end-stage KOA, as well as how responsive it is and how well it correlates with performance-based outcome measures after TKA. Methods: Patients on the waiting list for TKA performed SEBT in the anterior, posteromedial and posteriorlateral directions twice within 7 days. The measurements were repeated 6 and 12 months after TKA. The participants completed performance-based outcome measurements (PBOMs) and the Oxford Knee Score (OKS) before and after TKA to estimate correlation. Results: In all directions, the intraclass correlation coefficient range (ICC) was 0.998-0.993, and there were no significant differences between the test and re-test mean SEBT scores. The standard error of measurement (SEM) ranged from 0.37% to 0.68%, and the minimum detectable change (MDC) ranged from 1.02% to 1.89%. The post TKA SEBT results show significant improvement, with a large effect size. There were large-to-medium correlations between SEBT and PBOMs before and after TKA, while OKS correlated only before surgery. The magnitude of change in SEBT, PBOMs and OKS did not correlate. Conclusions: SEBT is an extremely reliable tool for assessing dynamic balance in all three directions of severe KOA patients. It is sensitive enough to detect balance changes at 6 and 12 months post TKA. SEBT cannot be used to reflect the change in functional outcome improvement after TKA.

Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.

The response to medical management of young dogs with osteoarthritis (OA) associated pain has not been evaluated. Using an open-label design, the effectiveness, over a 4-month period, of standardized management (grapiprant/fish oil/exercise) for treating OA pain in young dogs was evaluated.

Included dogs were 9 months-4 years of age; ≥3.6 kg body weight; had ≥1 appendicular joint with radiographic OA and obvious joint pain; had a Liverpool Osteoarthritis in Dogs (LOAD) score of ≥5. The non-steroidal anti-inflammatory piprant (grapiprant) was given at the recommended dose daily, omega-3 fatty acid supplementation was initiated at 100 mg/kg and then increased to 200 mg/kg daily, and leash exercise was gradually increased to a target of 60 min daily. Client-reported outcome measures (CROMs) and force plate gait analysis were collected at baseline and monthly for 4 months. The index limb was defined as the most severely affected limb at baseline.

Forty-eight dogs were enrolled (mean ± SD age of 30.7 ± 10.7 months). Hips, elbows, and stifles were commonly affected. Medication and supplement compliance was excellent (≥95% of target administered), and treatments were well-tolerated. CROMs showed significant improvement over time and at each time point. Overall, peak vertical force (PVF) increased significantly (<0.001), and vertical impulse increased numerically. Increase in PVF from baseline was significant at all time points except 4-months.

This study demonstrates a clinically meaningful benefit of a multimodal treatment regimen over a 4-month period for young dogs (<4 years old) with OA-pain. Future work should determine if early, effective treatment is of long-term benefit.

Osteoarthritis (OA) is the most common type of arthritis characterized by progressive cartilage degradation, with its pathogenesis closely related to chondrocyte autophagy. Chondrocytes are the only cells in articular cartilage, and the function of chondrocytes plays a vital role in maintaining articular cartilage homeostasis. Autophagy, an intracellular degradation system that regulates energy metabolism in cells, plays an incredibly important role in OA. During the early stages of OA, autophagy is enhanced in chondrocytes, acting as an adaptive mechanism to protect them from various environmental changes. However, with the progress of OA, chondrocyte autophagy gradually decreases, leading to the accumulation of damaged organelles and macromolecules within the cell, prompting chondrocyte apoptosis. Numerous studies have shown that cartilage degradation is influenced by the senescence and apoptosis of chondrocytes, which are associated with reduced autophagy. The relationship between autophagy, senescence, and apoptosis is complex. While autophagy is generally believed to inhibit cellular senescence and apoptosis to promote cell survival, recent studies have shown that some proteins are degraded by selective autophagy, leading to the secretion of the senescence-associated secretory phenotype (SASP) or increased SA-β-Gal activity in senescent cells within the damaged region of human OA cartilage. Autophagy activation may lead to different outcomes depending on the timing, duration, or type of its activation. Thus, our study explored the complex relationship between chondrocyte autophagy and OA, as well as the related regulatory molecules and signaling pathways, providing new insights for the future development of safe and effective drugs targeting chondrocyte autophagy to improve OA.

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.

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.

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.

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.

With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritis represents a multifactorial disease with no effective treatment options. As biomechanical shift in the trabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delay OA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models. We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and pain sensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase in subchondral bone volume and trabecular thickness with constant bone mineral density was found indicating favored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in control samples without magnesium. However, this result could not be confirmed by sensitive, objective lameness evaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degeneration evaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented results show a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevance regarding pain. Further studies with shifted focus should examine additional structures as joint capsule or osteophytes.

The objective of this manuscript was to carry out a comprehensive review of the published information on the use of Biopuncture in patients with knee osteoarthritis.

A scientific search was performed using online databases following the terms (Biopuncture) and (Knee Osteoarthritis) to identify scientific manuscripts that were related to the use of Biopuncture in the treatment of individuals with knee osteoarthritis.

With the information found, a theoretical framework was integrated that describes the components of Biopuncture, its mechanism of action and practical topics for the application of the technique.

Biopuncture appears to be a potential, simple and low-risk therapeutic strategy in the treatment of knee osteoarthritis, which is applied through periarticular subcutaneous injections, with multitarget mechanisms of action at various physiopathological levels such as the modulation of the inflammatory process, decreased peripheral sensitization, and stimulation of antidegenerative and trophic mechanisms. Perhaps it can be part of the integrative treatments for knee osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of joint cartilage, subchondral bone sclerosis, synovitis, and structural changes in the joint. Recent research has highlighted the role of various genes in the pathogenesis and progression of OA, with nuclear factor erythroid 2-related factor 2 (NRF2) emerging as a critical player. NRF2, a vital transcription factor, plays a key role in regulating the OA microenvironment and slowing the disease's progression. It modulates the expression of several antioxidant enzymes, such as Heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits the nuclear factor kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, joint pain, and the breakdown of cartilage extracellular matrix, while also mitigating cell aging and death. This review discusses NRF2's impact on oxidative stress, inflammation, cell aging, and various cell death modes (such as apoptosis, necroptosis, and ferroptosis) in OA-affected chondrocytes. The role of NRF2 in OA macrophages, and synovial fibroblasts was also discussed. It also covers NRF2's role in preserving the cartilage extracellular matrix and alleviating joint pain. The purpose of this review is to provide a comprehensive understanding of NRF2's protective mechanisms in OA, highlighting its potential as a therapeutic target and underscoring its significance in the development of novel treatment strategies for OA.

Temporomandibular joint (TMJ) pain and osteoarthritis (OA) are common and debilitating disorders that impair patients' quality of life. The mechanisms driving diseases-related pain are poorly understood, and current treatments fail to provide effective and long-term therapeutic effects. Additionally, pain assessment in research, particularly orofacial pain, poses several challenges that complicate studies in both clinical and basic science settings. Therefore, we have established an inflammatory TMJ pain mouse model via intra-articular injection of CFA (Complete Freund's Adjuvant) and evaluated pain behaviors by bite force measurement and the von Frey filament test. Mice with CFA injection exhibited orofacial pain behaviors compared to PBS injection, including reduced bite force and head withdrawal threshold in the von Frey filament test. These methods are relatively easy to execute to have reproducible results and can be potentially extended to pain studies for other disease models related to TMJ disorders. Together, bite force, and the von Frey filament tests are reliable in measuring orofacial pain, as demonstrated in CFA injection-induced painful TMJOA mouse models.

Intra-articular injection-based therapy is often used aside conservative treatment and lifestyle modifications to manage knee osteoarthritis (KO) patients. Conventional injections contain steroids and hyaluronic acid, while more recently multipotential adult stem cell, platelet-rich plasma (PRP), and platelet lysate (PL) injections have been used to promote cartilage regeneration or repair. The aim of the current study is to analyse current evidence on PL injections for the treatment of KO and to determine if these are effective and how these perform compared to other injection regimens. The databases of Scopus, Embase, PubMed, Web of Science, and Cochrane Library were searched on 30 June 2023. Risk of bias was assessed using the SYRCLE tool for animal studies and Cochrane RoB 2 as well as ROBINS-I tool for human studies. Studies were included if these were in English, any year, and regarded animals with osteoarthritis (OA) or human adult patients with OA. In vitro trials and non-adult human studies were excluded. Results on OA symptom stage and severity, and pain were recorded. The research retrieved three human studies (n = 48, n = 25, n = 58) and four animal studies: one rabbit, two studies, and one rat study. PL was found to decrease KO symptoms at follow-up ≤ 1 year with respect to baseline levels and when compared to hyaluronic acid or platelet-rich plasma. Symptoms returned 6 months-1 year after the final administration, with studies showing peak efficacy at approximately 6 months. Animal studies showed clinical improvements, reduction of lameness, and partial effect on the cartilage regeneration of the seven studies, two had a high risk of bias, four were associated to some concerns, and one had low risk. A major source of bias in these studies was the use of questionnaires and scoring that could be subject to interpretation. Overall, PL was well-tolerated and showed efficacy comparable to PRP; when pain control was assessed, it showed similar efficacy compared to hyaluronic acid. These findings may support its use in clinical trials to confirm these initial findings; future research should also focus on the comparison with other non-surgical treatments, on a more detail of the potential regenerative properties, and to optimise the treatment schedule.

To investigate the relationship between measures of radiographic joint space width (JSW) loss and magnetic resonance imaging (MRI)-based cartilage thickness loss in the medial weight-bearing region of the tibiofemoral joint over 12-24 months. To stratify this relationship by clinically meaningful subgroups (sex and pain status).

We analyzed a subset of knees (n ​= ​256) from the Osteoarthritis Initiative (OAI) likely in early stage OA based on joint space narrowing (JSN) measurements. Natural logarithm transformation was used to approximate near normal distributions for JSW loss. Pearson Correlation coefficients described the relationship between ln-transformed JSW loss and several versions of deep learning-derived MRI-based cartilage thickness loss parameters (minimum, maximum, and mean) in subregions of the femoral condyle, tibial plateau, and combined femoral and tibial regions. Linear mixed-effects models evaluated the associations between the ln-transformed radiographic and MRI-derived measures including potential confounders.

We found weak correlations between ln-transformed JSW loss and MRI-based cartilage thickness ranging from R ​= ​-0.13 (p ​= ​0.20) to R ​= ​0.26 (p ​< ​0.01). Correlations were higher (still poor) among females compared to males and painful compared to non-painful knees. Model results showed weak associations for nearly all MRI-based measures, ranging from no association to β (95% CI) ​= ​0.25 (0.11, 0.39). Associations were higher among females compared to males and minimal differences between painful and non-painful knees.

Despite its recommended use in disease-modifying OA drug clinical trials, results suggest that JSW loss is an ineffective proxy measure of cartilage thickness loss over 12-24 months and within a localized region of the tibiofemoral joint.