Pain in knee osteoarthritis (KOA) often shows a limited correlation with radiographic severity, complicating clinical assessment and highlighting the relevance of central pain mechanisms. Functional magnetic resonance imaging (fMRI) enables the investigation of brain regions such as the amygdala and nucleus accumbens, which are increasingly recognized as key components of the affective-motivational dimension of chronic pain and may show differential activation across clinical treatment contexts. This study is part of the HOLOA Project (Clinical and virtual examination of patients for holistic and objective description of the osteoarthritis progression mechanisms). We conducted a cross-sectional observational study nested within the HOLOA cohort. Thirty-one patients with KOA (20 managed conservatively [CM] and 11 observed in the surgical treatment context) with Kellgren Lawrence (KL) grades 2-3 were included. Participants underwent two fMRI paradigms involving pressure stimulation (Knee Interline and Tibial Surface tests). Clinical assessment included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Numeric Rating Scale (NRS). Group comparisons and correlation analyses were performed to examine associations between clinical measures and brain activation patterns. Groups were broadly comparable with no statistically significant differences in demographic or radiographic severity measures. These patients showed higher WOMAC and PCS scores, indicating greater functional impairment and pain catastrophizing. Across the whole cohort, painful stimulation elicited robust activation of classical pain-processing regions, while no significant amygdala or nucleus accumbens activation was observed at the group level. However, nucleus accumbens activity was positively associated with PCS scores. In between-group analyses, patients observed in the surgical treatment context exhibited significant bilateral amygdala activation during Tibial Surface stimulation, which was absent in the conservatively managed group, and reported higher post-test NRS scores. Limbic system activation and pain catastrophizing were associated with the surgical treatment context in patients with knee osteoarthritis within a similar range of radiographic severity. The observed involvement of the amygdala and nucleus accumbens underscores the relevance of affective-motivational and cognitive processes in chronic KOA pain. These findings support the value of integrating clinical, psychological, and neurobiological perspectives when interpreting symptom burden and treatment context in knee osteoarthritis.
Osteoarthritis (OA) is a degenerative joint disease characterized. The Mini-Osteoarthritis Knee and Hip Quality of Life (Mini-OAKHQoL) scale is used to evaluate the impact of knee/hip osteoarthritis (KOA/HOA) on patients' quality of life (QoL). This study aims to ascertain the consistency and accuracy of the Mini-OAKHQoL Syrian Arabic version. This cross-sectional study translated the original version of the Mini-OAKHQoL into Syrian Arabic using a standard method for language adjustment. The patients completed the Syrian Arabic version and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Short Form-36 (SF-36) scales. The psychometric properties of the Syrian Arabic Mini-OAKHQoL were evaluated using Cronbach's α for internal consistency, intraclass correlation coefficient (ICC) for test-retest reliability, and Spearman's correlation coefficient for convergent validity. Statistical significance was set at p < 0.05. This study included 87 persons with KOA/HOA. The Mini-OAKHQoL demonstrated satisfactory face and content validity. The intraclass correlation coefficient, confidence intervals (ICC = 0.844, 95% CI: 0.76-0.90). for the overall score with a cut-off > 0.5. The Cronbach's α for the categories was satisfactory internal consistency (α > 0.7). Regarding the assessment of convergent validity, physical activities, mental health, pain, and independent items of the Mini-OAKHQoL Arabic version demonstrated moderate to high correlations with the WOMAC and SF-36. The Mini-OAKHQoL is a well-validated and reliable scale for evaluating QoL in patients with KOA/HOA, demonstrating strong utility in both clinical practice and research settings among Arabic-speaking populations.
[Purpose] This case series aimed to evaluate the effects of a standardized exercise dosage using a cycle ergometer on body weight and patient-reported outcome measures among overweight female patients with knee osteoarthritis. [Participants and Methods] We conducted a two-phase study. Exercise dosage was standardized using kilocalories per kilogram of body weight per week. Study 1 verified the feasibility and safety of progressive dosage in a single participant, while Study 2 used an ABCB-type single-case design involving three participants. The participants performed a cycle ergometer exercise with standard physical therapy. Body weight was the primary outcome, and the Japan Knee Osteoarthritis Measure was the secondary outcome. [Results] In Study 1, the participant safely achieved an energy expenditure of up to 10 kilocalories per kilogram of body weight per week; however, symptoms resembling knee buckling occurred at an expenditure of 11 kilocalories per kilogram of body weight per week. In Study 2, no adverse events were observed. One participant significantly reduced body weight during Phase B2, and all participants exhibited an improvement in Japan Knee Osteoarthritis Measure scores. [Conclusion] Standardized exercise dosage based on kilocalories per kilogram of body weight per week provides a safe and effective method for overweight female patients with knee osteoarthritis.
Background/Objectives: Osteoarthritis has been increasingly described as associated with systemic inflammation, raising the question of how it would affect fertility in young women with or without reproductive hormone administration. We studied oogenesis in mice with collagenase-induced osteoarthritis (CIOA) as a model system with fewer ethical limitations after estradiol (E2) or follicle-stimulating hormone (FSH) treatment. Methods: Oocytes have been isolated from mice subjected to various treatment regimens. The meiotic spindle, the chromatin, and the actin cap were fluorescently labeled and analyzed. Results: In addition to reduced maturation rates, specific oocyte abnormalities were registered when CIOA, FSH, or E2 were applied in isolation. Combined treatments showed that the spindle, chromatin, and actin cytoskeleton parameters were differently affected in oocytes from groups with CIOA treated by estradiol and those treated with FSH. Enlarged spindles, ooplasmic tubulin asters, aligned metaphases, and predominantly normal actin caps, often with an actin halo, were typical for groups with CIOA combined with estradiol. The groups with CIOA and FSH had slightly enlarged spindles, unaligned metaphases with degenerated chromatin surrounded by a cloud of depolymerized tubulin, and small actin caps. Conclusions: Our results show that experimental osteoarthritis with or without exogenous reproductive hormones negatively affects oogenesis, presumably due to systemic inflammatory factors making the ovarian microenvironment less capable of supporting oocyte maturation. Estradiol supplementation does not benefit oogenesis. FSH treatment induced cytoskeletal and chromatin abnormalities that presumably disturb the fertilization and development potential of affected oocytes. These data can have implications for assisted reproduction in cases of patients with osteoarthritis.
Sacroiliac joint (SIJ) disorders are among the most common causes of chronic low back pain. Imaging-guided SIJ injections are widely used as an early diagnostic tool, with corticosteroid often added to provide a therapeutic component. Evidence of factors predicting the therapeutic outcome of these injections remains scarce. To evaluate the effect of SIJ osteoarthritis and other potentially relevant demographic, imaging, and procedural factors on the patient-reported therapeutic outcome of imaging-guided SIJ injection. This retrospective single-center study included 101 patients who underwent specialist-referred imaging-guided SIJ injection between 2010 and 2023. Medical records and procedural reports were reviewed to collect relevant patient information, and associated SIJ MRIs and CT scans were reanalyzed for osteoarthritis, sacroiliitis, and bone marrow edema by an experienced musculoskeletal radiologist. The association of demographic, imaging, and procedural factors with the therapeutic injection outcome was assessed using logistic regression modeling. Of 101 patients who underwent an imaging-guided SIJ injection, 72 (71.3%) met the inclusion criteria. The mean age was 52.2 (SD 14.2) years, and 30 patients (41.7%) achieved a positive therapeutic response. Increasing age was significantly associated with a lower likelihood of a positive outcome, with the probability decreasing on average by 9.4% for each additional year of age (OR 0.91 [95% CI 0.84-0.99]). Neither SIJ osteoarthritis grade nor other demographic, imaging, or procedural factors showed a significant association with injection outcome. Increasing age was significantly associated with a lower likelihood of achieving a positive therapeutic SIJ injection outcome, while SIJ osteoarthritis grade showed no association.
Osteoarthritis is characterized by cartilage degradation and joint distortion. The most prevalent version of osteoarthritis, knee osteoarthritis (KOA), affects millions, acting as a leading cause of disability. With the average life expectancy continuing to grow, the global burden of KOA is expected to increase. KOA involves chronic pain that limits function and adversely impacts patients' quality of life. Long-term management is costly and burdensome, often requiring continuous treatment that only delays disease progression unless patients receive a total knee arthroplasty. Recently, traditional treatment modalities for KOA have been augmented by advancements in machine learning (ML), which enable automated disease grading, predictive modeling for early diagnosis, and personalized treatment strategies, alongside growing interest in stem cell-based therapies. With the goal of developing less invasive treatments that slow or reverse KOA progression, investigation into these novel therapies have increased. Stem cell-based therapies offer the potential to modulate inflammation, reduce pain, and preserve cartilage integrity, addressing key limitations of existing treatments. Mesenchymal stem cells have shown promising preclinical and clinical results, demonstrating improvements in pain, function, and cartilage-related outcomes through immunomodulatory and paracrine mechanisms. This narrative review synthesizes current evidence on conventional and emerging therapies for KOA, with a dual focus on ML-driven clinical applications and stem cell-based regenerative strategies, and discusses their potential roles in improving diagnosis, treatment selection, and patient outcomes. While further research is needed to understand the full potential of stem cells for treating KOA, these promising findings make it a useful topic for current and future clinical applications.
Objectives: The aim of this study was to evaluate the psychometric properties of the Pain Catastrophizing Scale (PCS) in patients with carpometacarpal osteoarthritis of the thumb. Methods: In this cross-sectional register-based study of 253 patients with carpometacarpal osteoarthritis of the thumb, a two-parameter item response theory analysis was used to evaluate the items' difficulty and discrimination parameters. Results: Of 253 patients, 245 (57%) were women. The mean age was 56.0 (SD 16.5) years. The mean total PCS score was 14.0 (SD 10.5) points. Difficulty estimates were distributed fairly evenly across the item score scale, with a slight shift towards higher scores. Discrimination of both total and subscale scores was perfect, varying from 1.91 to 2.84. Conclusions: PCS was able to discriminate well between different levels of catastrophizing. PCS performed slightly more accurately when the catastrophizing level was above average in the studied sample. PCS can be recommended for clinical use when assessing catastrophizing in patients with carpometacarpal osteoarthritis of the thumb.
Background: Care for knee osteoarthritis (KOA) is frequently fragmented, and pathway-level decisions within Physical Medicine and Rehabilitation (PM&R) are influenced by local organizations. The objective of this study was to identify areas of agreement and disagreement among PM&R experts and to translate these into a clinically interpretable, function-oriented care pathway for knee osteoarthritis (KOA) within rehabilitation services. Methods: A two-round Real-Time Delphi study was conducted using the SmartDelphi web platform. A steering committee of five PM&R physicians developed a 37-item questionnaire covering referral/access, functional and outcome assessment, conservative management, escalation/referral thresholds, and follow-up/discharge. Round 1 was online (SERMEF osteoarthritis working group; 46 invited, 40 completed; 87.0%) with responses collected until 30 April 2025. Round 2 was an in-person, facilitated validation round on 30 May 2025 at the SERMEF Congress (A Coruña; 85 invited, 70 completed; 82.4%). Items were rated on a 6-point Likert scale; consensus strength was defined by interquartile range (IQR): strong (0-1) vs. weak (≥2). No patient-level data were collected; participant characteristics were comparable across rounds, suggesting consensus refinement reflected deliberation rather than panel shifts over time. Results: Consensus supported a longitudinal, function-first pathway that was structured into five phases: entry/referral to PM&R; comprehensive functional assessment using a minimum outcomes dataset (pain VAS/NRS, WOMAC function, quality-of-life scale); multimodal conservative rehabilitation combining exercise/physiotherapy, education/self-management support, and indicated oral/topical therapies; reassessment-guided escalation in non-responders, reserving interventional PM&R techniques, multidisciplinary musculoskeletal pain-unit management, or orthopedic evaluation for persistent pain and/or functional limitation; and longitudinal monitoring with defined discharge criteria. Conclusions: SERMEF PM&R experts converged on an implementation-oriented, outcomes-driven KOA itinerary centred on functioning, conservative multimodal care, structured reassessment, and explicit discharge planning.
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage destruction, and chondrocyte apoptosis plays a critical role in TMJOA progression. As chondrocytes reside in an avascular microenvironment inside the cartilage matrix, energy production via glycolysis is crucial for their survival. This study investigated the role of the key glycolytic enzyme Hexokinase 2 (HK2) in TMJOA pathogenesis and the therapeutic potential of dental pulp stem cell-derived extracellular vesicles (DPSC-EVs). In a rat experimental TMJOA model induced by monosodium iodoacetate (MIA) intra-articular injection, we observed a significantly decreased expression of HK2 along with cartilage matrix degradation. In the in vitro study, MIA induced chondrocyte apoptosis with caspase-3 activation, accompanied by impaired glycolytic function. Intervention with DPSC-EVs effectively rescued the expression of HK2 within chondrocytes, leading to a notable restoration of cellular glycolysis. Consequently, DPSC-EV treatment markedly attenuated the progression of TMJOA by reducing chondrocyte apoptosis and improved cartilage integrity. Our findings demonstrated that DPSC-EVs represent a promising cell-free therapeutic strategy for TMJOA, exerting their protective effects by targeting HK2, thereby preserving chondrocyte viability and attenuating osteoarthritis development.
Knee osteoarthritis (KOA) is a leading cause of chronic pain and disability in humans, companion and farm animals, with socioeconomic burden and animal welfare concerns. KOA models are essential for advancing diagnostics, therapies, and preventive strategies. This study aimed to establish a reliable non-invasive rat KOA model and evaluate its translational value for comparative and clinical medicine. Twenty male Sprague-Dawley rats were randomly allocated to two groups: a model group (n = 10) and a control group (n = 10). KOA was induced in the model group by immobilizing the knee joint through circular fixation using a medical polyurethane composite bandage. Following the modeling phase, knee cartilage was macroscopically evaluated. Functional impairment was assessed using the Modified Lequesne MG scale. Imaging analyses comprised 7.0 T magnetic resonance imaging (MRI) and micro-computed tomography (Micro-CT) to examine structural and morphological alterations in the knee joint. The histological assessment included Safranin O-Fast Green staining to assess cartilage degradation using the Osteoarthritis Research Society International (OARSI) scoring system. Chondrocyte apoptosis was identified through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The examination of the knee joint cartilage in the model group revealed significant surface irregularities and roughness. Compared to the control group, the model group exhibited a notably higher Modified Lequesne MG score (P < 0.01), indicating compromised joint function. Imaging techniques such as high-field MRI and micro-CT confirmed typical osteoarthritic characteristics. Safranin O-Fast Green staining showed a substantial reduction in proteoglycans in the superficial cartilage layer of the model group, along with a significantly increased OARSI score (P < 0.01). TUNEL staining indicated a marked rise in chondrocyte apoptosis in the model group, with an approximately 4.8-fold higher rate compared to the control group (P < 0.01). The model induction success rate exceeded 95%, with a complication rate below 5%. We developed a non-invasive rat KOA model using polyurethane bandage immobilization that recapitulates cross-species progressive OA pathology. This robust, low-cost platform enables early biomarker screening, disease-modifying therapy evaluation, and preventive intervention validation for veterinary/human OA, highlighting its translational value for comparative and clinical medicine.
Knee osteoarthritis (KOA) is a degenerative bone and joint disease. Jingu Zhitong Gel (JGZTG) exhibits a promising therapeutic effect in the clinical treatment of knee osteoarthritis (KOA). However, the mechanism of JGZTG in treating KOA remains unclear. We established a rat model of KOA through surgery and treated rats with JGZTG for 21 days. The pain threshold was measured by the Ugo Basile joint pain tester, the weight bearing on the right foot was detected by a bipedal balance tester, the inflammatory factor levels were measured by ELISA kits, and the joint morphology score was evaluated. Hematoxylin and eosin staining (H&E) was used to evaluate the pathological lesions, while toluidine blue staining was used to observe the proteoglycan depletion. Transcriptomic analysis was conducted to elucidate the potential mechanisms of JGZTG in treating KOA. Real-time quantitative Polymerase Chain Reaction (RT-qPCR), and immunofluorescence (IF) assays were conducted to validate transcriptomic results and investigate the analgesic mechanisms. After 21 days of treatment, JGZTG significantly increased the pain threshold and the weight bearing on the right foot in KOA rats, furthermore, reduced the levels of inflammatory factors (TNF-α, IL-6, IL-1β, and PGE2) in the serum and joint lavage fluid. In addition, JGZTG significantly decreased the joint morphology score, reduced synovial damage, alleviated cartilage injury, and reduced proteoglycan depletion in KOA models. The results of transcriptomic analysis showed that the anti-inflammatory effect of JGZTG in treating KOA was associated with the IL-17 signaling pathway. Further validation revealed that the relative mRNA and protein expression of IL-17RB, FosB, MMP1b, MMP3, MMP13, CCL17, and CXCL6 were regulated by JGZTG. In addition, JGZTG can reduce the mRNA and protein overexpression of NGF, Ntrk1, Trpv1, Ptgs2, PGE2, EP4, TAC1, and Calca, which are the key factors of the NGF-TrkA and COX-2/PGE2 pathways. JGZTG exhibits pain-relieving and anti-inflammatory effects in KOA, which were linked to altered IL-17, NGF-TrkA, and COX-2/PGE2 pathways. These findings have provided experimental evidence for the mechanisms underlying the therapeutic effects of JGZTG in KOA.
Background and Objectives: Knee osteoarthritis (KOA) is a major cause of global disability. The efficacy of a non-invasive treatment, pulsed electromagnetic field (PEMF) therapy, remains debated. This systematic review and meta-analysis evaluate PEMF's effectiveness on KOA, exploring the influence of device parameters. Materials and Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) from 2015 to 2025. Nine RCTs with a total of 457 patients were included. Primary outcomes were pain (Visual Analog Scale-VAS) and function (Western Ontario and McMaster Universities Osteoarthritis Index-WOMAC). Data were pooled using a random-effects model with subgroup analyses based on PEMF amplitude and frequency. Results: No significant improvement in VAS pain or total WOMAC scores was found at one month. However, time-dependent effects were observed. WOMAC-pain improved significantly at 18-21 days (MD = -1.63, 95% CI: -2.43 to -0.82, I2 = 28%) but not at one month. Conversely, WOMAC-stiffness (MD = -1.11, 95% CI: -1.386 to -0.85, I2 = 0%) and daily activity (MD = -3.39, 95% CI: -4.81 to -1.97, I2 = 0%) improved significantly only at the one-month. Objective functional measures did not improve, and the overall risk of bias across studies was high. The efficacy of PEMF is also influenced by the amplitude and frequency. Conclusions: PEMF efficacy for KOA is nuanced, with benefits dependent on timing and device parameters. High frequency gives fast pain relief; high amplitude builds function. Though statistically significant, these improvements may not reach thresholds for clinical meaningfulness. Significant heterogeneity in treatment protocols is a major barrier to clear conclusions. Standardized, large-scale RCTs are needed to determine optimal parameters and confirm PEMF's clinical role.
Knee osteoarthritis (KOA) is a prevalent condition associated with pain and reduced physical function worldwide, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is one of the most commonly used disease-specific patient-reported outcome measures. Its use in non-English-speaking populations requires appropriate translation and validation, and no validated Kazakh version has previously been available. This study aimed to translate, culturally adapt, and evaluate the psychometric properties of the Kazakh version of the WOMAC in patients with KOA. A cross-sectional validation study was conducted among 452 patients with clinically diagnosed KOA and 126 healthy individuals, following established international guidelines. The study assessed internal consistency, test-retest reliability, construct validity, content validity, convergent validity, known-groups validity, and floor and ceiling effects. The Kazakh WOMAC demonstrated acceptable to high internal consistency (Cronbach's α = 0.77-0.88) and good test-retest reliability (ICC = 0.78-0.83). Content validity was excellent (S-CVI/Ave = 0.96), and confirmatory factor analysis supported the original three-factor structure. Expected correlations with SF-36 domains confirmed convergent validity, and WOMAC scores differentiated patients with KOA from healthy individuals, with no relevant floor or ceiling effects observed. The Kazakh version of the WOMAC is a reliable and valid instrument for assessing pain, stiffness, and physical function in Kazakh-speaking patients with KOA.
The treatment of severe osteoarthritis of knee with proximal tibia stress fracture is daunting. There is no palpable treatment guideline for this condition. This study evaluates the functional and radiological outcomes of single staged long tibial stem total knee arthroplasty. In this retrospective cohort, 10 patients were enrolled with severe osteoarthritis of knee with tibia stress fracture from 2020 to 2023. All patients were operated with posterior stabilising long tibial stem total knee arthroplasty. Pre-operative and post-operative functional and radiological assessments were evaluated. The follow-up period ranged from 16 to 28 months, with a mean of 21 months. 15.2° varus was the average HKA angle (SD 3.68°). Knee range of motion increased from 106° (range 90 - 115°) to 127° (range 120 - 130°), while FFD improved from 16° (range 5 - 30°) to 1.5° (range 0 - 5°). Both the mean Knee Society score, and its functional score increased from 21.5 (range 5-35) to 78 (range 65-90) (p<0.001) and from 21.7 (range 4-42) to 89.3 (range 82-95) (p<0.001), respectively. All patients had fracture union during a follow-up period of three to six months (mean 3.90 months). Stress fracture in not uncommon in elderly osteoarthritic patients, long tibial stem total knee replacement provides safe and sublime result. Extension rod provides better restoration of alignment and facilitates fracture healing.
To identify synovial transcriptional clusters in human knee osteoarthritis (OA) and determine how these relate to synovial histologic features, cell-type-associated gene expression, and cartilage degeneration severity. Bulk RNA sequencing (RNA-seq) of synovial tissue from n = 135 patients with knee OA was analyzed using consensus clustering. Clusters were compared by clinical and histologic features, including cartilage degeneration severity (OARSI score). Single-cell RNA-seq (n = 18) and spatial transcriptomics were used to relate cartilage degeneration-associated gene expression patterns to synovial cell populations. Four synovial transcriptional clusters that differed in synovial histologic features and cartilage degeneration severity were identified. Greater cartilage degeneration was associated with enrichment of lining fibroblast- and inflammatory myeloid-associated gene expression, whereas lesser cartilage degeneration was associated with enrichment of sublining fibroblast, endothelial, mural cell, and adipocyte-associated gene expression. Human knee OA synovium segregates into transcriptional clusters associated with cartilage degeneration severity. Synovial transcriptional heterogeneity corresponds to cell-type-associated gene expression. What is already known on this topic: Osteoarthritis synovium exhibits marked histologic and molecular heterogeneity.Synovial inflammation detected by MRI correlates with cartilage degeneration and predicts progressive cartilage loss in knee OA.Prior transcriptomic studies have identified molecular subsets of OA synovium, but their relationship to cartilage degeneration severity remains unclear.What this study adds: OA synovium segregates into four transcriptional clusters: Sublining (C1), Lymphomyeloid (C2), Myeloid (C3), and Major trauma (C4).Greater cartilage degeneration is associated with enrichment of inflammatory myeloid and lining fibroblast gene expression, whereas lesser degeneration is associated with enrichment of adipocyte, sublining fibroblast, endothelial, and mural cell-associated gene expression.How this study might affect research, practice or policy: Provides a framework for a clinically relevant biological stratification of OA patients based on synovial molecular features.Informs future efforts to link synovial biology with OA prognosis, cartilage degeneration, treatment allocation, and development of targeted therapeutic strategies.
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients' quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA.
Background and objectives: Articular cartilage provides low-friction articulation across joint surfaces, distributes loads, and absorbs stress, all of which are crucial mechanical functions of joints. Changes in the mechanical characteristics of cartilage are among the first signs of degenerative joint disease, and they are especially important for athletes who are subjected to high-impact, high-magnitude loading on a regular basis. The objective of this study was to: (i) compare the mechanical characteristics of tibiofemoral cartilage in healthy and osteoarthritic conditions across medial and lateral anatomical compartments; and (ii) use nonlinear phenomenological viscoelastic modeling in conjunction with unconfined compression testing to characterize compartment-specific viscoelastic behavior. Materials and Methods: Forty-six human tibiofemoral cartilage samples were collected during knee surgeries and classified as healthy (n = 17) or osteoarthritic (n = 29) and as medial (n = 26) or lateral (n = 20). Quasi-static unconfined compression tests were performed at 1 mm/min to obtain stress-strain responses, Young's modulus, maximum compressive stress, and energy absorption. Viscoelastic behavior was analyzed using a nonlinear phenomenological viscoelastic model. Appropriate parametric or non-parametric statistical tests and effect size measures were applied. Results: Osteoarthritic cartilage's stiffness and energy absorption were significantly higher than those of healthy tissue (p < 0.05). Medial cartilage exhibited significantly greater stiffness and stress than lateral cartilage (p < 0.001). The nonlinear phenomenological viscoelastic model provided an excellent fit (R2 > 0.999). Conclusions: The mechanical profile of osteoarthritic tibiofemoral cartilage is characterized by pathological mechanical remodeling and increased stiffness. Greater mechanical susceptibility in the medial compartment supports the significance of cartilage biomechanical properties as sensitive indicators of early degeneration and osteoarthritis risk in athletic populations.
Osteoarthritis (OA) is a complex degenerative joint disease for which early diagnosis and clear molecular characterization remain limited. DNA methylation has been increasingly recognized as an important regulatory factor in OA pathogenesis. In this study, we proposed an integrative computational framework combining statistical analysis, machine learning, deep learning, and functional genomics to identify and validate OA-associated genes and methylation biomarkers for diagnostic and biological interpretation. Candidate CpG sites were obtained using two complementary strategies: differential methylation analysis and selection of loci located near transcription start sites of previously reported OA-related genes. Key features were further refined using support vector machine recursive feature elimination and random forest algorithms. Based on the selected loci, we developed a feature-fusion diagnostic model that combines Transformer and convolutional neural networks with adaptive weighting to capture both global dependency structures and local methylation patterns. A panel of 220 methylation sites demonstrated stable and reproducible diagnostic performance in an independent cohort. Functional annotation and pathway analysis highlighted several established OA-associated genes, including TGFBR2, SMAD3, PPARG, and MAPK3, and suggested INHBB as a potential novel effector gene, with additional support for AMH and INHBE involvement. Overall, this study presents a robust methylation-based framework for identifying key OA-associated genes and provides new insights into the epigenetic mechanisms underlying OA.
Osteoarthritis (OA) is characterized by a chronic inflammatory microenvironment accompanied by elevated reactive oxygen species (ROS), synovial immune dysregulation, and progressive cartilage degeneration. While conventional pharmacological treatments often exhibit limited efficacy in halting disease advancement, we report a biomimetic, ROS-responsive nanoparticle (NPs) delivery system coated with macrophage membranes (MM-shTHY1-NPs) to achieve targeted therapy. The macrophage membrane (MM) coating not only improves retention and targeting toward inflamed synovial tissues, but also provides cytokine-scavenging capability that helps buffer the inflammatory microenvironment. Within the oxidative joint microenvironment, the ROS-responsive architecture of the NPs-facilitated by diselenide bonds-triggers the site-specific release of shTHY1 payloads. Importantly, we demonstrated the therapeutic relevance of THY1 silencing in OA microenvironment remodeling; both in vitro and in vivo experiments demonstrate that shTHY1 delivery effectively promotes macrophage repolarization from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. This phenotypic shift subsequently remodels the chondrocyte microenvironment, suppressing matrix metalloproteinase expression and attenuating cartilage degradation. The synergy between RNAi-mediated THY1 silencing and the cytokine-scavenging capability of the macrophage membrane coating resulted in enhanced therapeutic efficacy. Our findings suggest that this cell-membrane-coated nanoplatform provides a promising strategy for the treatment of inflammatory joint diseases, with potential advantages in biosafety, site-specific delivery, and translational feasibility.
Knee osteoarthritis (OA) is a chronic, degenerative joint disorder characterized by cartilage deterioration and persistent pain. Currently, there are no disease-modifying drugs and pharmacological treatments are unsatisfactory for OA. To investigate the therapeutic effects of whole-body vibration (WBV), a nondemanding physical intervention, on pain behaviors and cartilage morphology in male and female mice with knee OA. A medial meniscal transection (MMT) was used as a model that mimics meniscal tear-induced knee OA in patients. Animals were exposed to WBV (15-Hz frequency, 332-µm amplitude, 0.3g acceleration) for 15 minutes per day, 5 days per week, for 13 weeks, beginning 3 weeks after MMT, using a custom-made WBV device. Behavioral analysis included assessment of mechanical sensitivity (by von Frey filaments), the hind limb use (by dynamic weight-bearing), heat sensitivity (by Hargreaves test), locomotor activity (in open field boxes), and body weight. Microcomputed tomography was used to examine cartilage morphology. Medial meniscal transection triggered mechanical hypersensitivity, reduced OA limb use, and induced cartilage damage in the medial and lateral compartments of femur and tibia, in both sexes. Whole-body vibration substantially alleviated mechanical hypersensitivity and improved limb use for up to 4 months after MMT, without affecting heat sensitivity, locomotor activity, or body weight. Furthermore, WBV considerably reduced the percentage of subchondral bone denuded of cartilage and increased cartilage thickness in the femur and tibia. These findings highlight the therapeutic potential of WBV as a nonpharmacological approach to relieve pain and restore cartilage integrity in knee OA.