Stages Of Osteoarthritis Research Articles

LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes

We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration.

Identification and characterisation of temporal abundance of microRNAs in synovial fluid from an experimental equine model of osteoarthritis.

MicroRNAs, a class of small noncoding RNAs, serve as post-transcriptional regulators of gene expression and are present in a stable and quantifiable form in biological fluids. MicroRNAs may influence intra-articular responses and the course of disease, but very little is known about their temporal changes in osteoarthritis. To identify miRNAs and characterise the temporal changes in their abundance in SF from horses with experimentally induced osteoarthritis. We hypothesised that the abundance of miRNA would change during disease progression. In vivo experiments. RNA extracted from synovial fluid obtained sequentially (Day 0, 28 and 70) from nine horses with experimentally induced osteoarthritis was subjected to small RNA sequencing using the Illumina Hiseq 4000 sequencing platform. Differentially abundant miRNAs underwent further validation and mapping of temporal abundance (Day 0, 14, 17, 21, 28, 35, 42, 49, 56, 63 and 70 days after osteoarthritis induction) by microfluidic reverse transcription quantitative real-time PCR. Bioinformatic analyses were performed to predict potential biological associations and target genes of the differentially abundant microRNAs. Small RNA sequencing revealed 61 differentially abundant microRNAs at an early osteoarthritis stage (Day 28), and subsequent reverse transcription quantitative real-time PCR analysis validated 20 of these. Significant biological functions of the differentially abundant microRNAs were apoptosis, necrosis, cell proliferation and cell invasion. Following validation, four microRNAs (miRNA-199b-3p, miRNA-139-5p, miRNA-1839 and miRNA-151-5p) were detected in more than 50% of the synovial fluid samples and had higher abundance in osteoarthritic than in control joints. Limited sample size. This is the first study to determine longitudinal changes in synovial fluid microRNA abundance in an equine model of osteoarthritis. Larger studies are needed in naturally occurring osteoarthritis to interrogate putative changes identified by this study.

Alleviating osteoarthritis-induced damage through extracellular vesicles derived from inflammatory chondrocytes.

The role of extracellular vesicles (EVs) derived from inflammatory chondrocytes in EV-based therapy for osteoarthritis (OA) has received little attention. We examined the effects of EVs derived from both normal rat chondrocytes (nEVs) and IL-1β-treated rat chondrocytes (iEVs) on IL-1β-treated rat chondrocytes, macrophages, and osteoblasts, alongside mRNA-seq and miRNA-seq analyses of both them. Additionally, nEVs and iEVs were administered intra-articularly in the joints of rat models subjected to anterior cruciate ligament transection (ACLT), and the morphological alterations across the joints were assessed. These findings indicated that iEVs, compared with nEVs, significantly enhanced collagen II synthesis in IL-1β-treated chondrocytes, accompanied by marked increases in ER stress and autophagy. In comparison to nEVs, iEVs exhibited a greater effect on facilitating M2-type macrophage polarization while simultaneously diminishing M1-type polarization, a process likely mediated by the downregulation of chemotactic cytokines such as Cxcl10, Ccl5, Cxcl9, Cxcl1, and Cxcl11. iEVs exerted a more pronounced influence on the phenotypic characteristics of IL-1β-treated osteoblasts than nEVs. In the ACLT-rat model, iEVs, akin to nEVs, effectively mitigated articular cartilage degradation. However, there was no significant difference in OARSI Scores between the two groups, despite iEVs exerting a greater effect on increasing hyaline cartilage thickness and proteoglycan content. iEVs were superior to nEVs in attenuating synovium inflammation and promoting trabecula formation in the femur subchondral bone. Consequently, iEVs, akin to nEVs, significantly alleviated OA-induced damage. Moreover, iEVs outperformed nEVs in certain aspects, notably in augmenting hyaline cartilage, reducing synovium inflammation, and promoting trabecular formation in the subchondral bone during the early stage of OA.

Similar efficacy of intra-articular hyaluronic acid injections and other biologically active injections in patients with early stages knee osteoarthritis: a level I meta-analysis.

The present meta-analysis compared the efficacy of intra-articular hyaluronic acid (HA) injections in patients with early to mild knee osteoarthritis (OA) (Kellgren Lawrence I-II) versus other commonly injected biologically active compounds using patient-reported outcome measures (PROMs). The outcomes of interest were the visual analogue scale (VAS) and the Western Ontario McMaster Osteo-Arthritis Index (WOMAC) scores. This study was conducted according to the 2020 PRISMA statement. In April 2024, PubMed, Web of Science, Google Scholar, and Embase were accessed without time constraints. All the randomised controlled trials (RCTs) investigating the efficacy of intra-articular HA injections in the early stages of knee OA were accessed. Data concerning the VAS, WOMAC, and related subscales were collected at baseline and the last follow-up. Only studies clearly stated the degrees of advancement of OA using the Kellgren-Lawrence scoring system were used. The literature search resulted in four RCTs (390 patients). The mean length of the last follow-up was 7.5 ± 3.0months. 72.3% (282 of 390) of the patients were women. The mean age of the patients was 58.1 ± 3.2years, and the mean BMI was 27.3 ± 3.2kg/m2. At the last follow-up, no difference was found between HA and the control group in VAS, WOMAC, and related subscales. In patients with early to mild knee osteoarthritis, the current level of evidence suggests that intra-articular injections using HA performed similarly to other biologically active compounds commonly injected in the knee joint for a minimum of three months. Level I, meta-analysis.

Enhanced Pain Reduction at Different Stages of Knee Osteoarthritis via Repeated Injections of Hyaluronic Acid with Niacinamide: A Comparative Study.

Background: Osteoarthritis (OA) of the knee is the most common joint disease, characterized by the degeneration of joint cartilage. Intra-articular hyaluronic acid (IAHA) injections are a well-established non-surgical treatment. Methods: This retrospective study analyzed knee OA patients receiving IAHA combined with niacinamide injections, assessing pain reduction in relation to patient data, the number of injections, and radiological findings. Results: IAHA injections led to significant pain reduction on the numeric rating scale (NRS) (0-10), with a mean decrease of 3.34 ± 1.65. Pain relief was greater with multiple injections. A comparison of subgroups by injection frequency (1, 2, or >2) showed significant pain reduction between 1 and 2 injections (p = 0.027) and between 1 and >2 injections (p = 0.032). The OA grade measured using the Kellgren-Lawrence (p = 0.95) and Vallotton MRI classifications (p = 0.50) did not correlate with pain reduction. However, patients with meniscal damage (p = 0.02) showed a greater benefit. A strong positive correlation was found between baseline pain intensity and pain reduction (p < 0.001; r = 0.61). Conclusions: IAHA with niacinamide significantly reduces knee OA pain, with more injections enhancing pain relief. Greater benefits were observed in patients with higher baseline pain and meniscal damage. The favorable safety profile and potential for repeated treatments make IAHA a valuable option in knee OA management.

Relationship Between the Subchondral Trabecular Bone Microstructure in the Hip Joint and Pain in Patients with Hip Osteoarthritis.

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.

Correlation between Q angle and hip abductor muscle strength in patients with knee osteoarthritis

BackgroundThe Q angle has a major impact on the lower limb’s static alignment in the frontal plane; also, the lever-arm distance between the hip and knee joint centers also changes the hip abductor muscles’ ability to produce torque. An association between Q angle and hip muscle strength has been investigated in different population. However, the relationship between Q angle and hip abductor muscle strength in early knee osteoarthritis has not been investigated. Therefore, the objective of the study was to investigate the correlation between Q angle and hip abductor muscle strength in patients with initial stage of knee osteoarthritis (OA).Study designThis is a correlation study.MethodologyFifty-four involved OA knee among 32 patients (26 female and 6 male), with mean age of 49.38 ± 5.68 years, were included in the study. The Q angle was measured by universal goniometer, and the hip abductor muscle strength was measured by a hydraulic handheld dynamometer.ResultsSpearman’s correlation coefficient test showed that Q angle is significantly (weak negative) correlated (r = − 0.31; p < 0.05) with hip abductor muscle strength, in patients with knee osteoarthritis.ConclusionThere is a correlation between Q angle and hip abductor muscle strength in patients with knee OA. So, with the decrease in hip abductor, muscle strength may lead to increase in Q angle, which may be a factor responsible for early-stage degenerative changes in knee OA.

Denervation of the Patella During Knee Arthroplasty: An Updated Systematic Global Review.

Background: Total knee arthroplasty is a widely endorsed surgical intervention, extensively recognized within the orthopedic field for its efficacy in significantly reducing pain and enhancing overall mobility in patients suffering from advanced stages of osteoarthritis. Despite a general consensus on the core procedural steps, the rapid advancements in implant technology and the nuanced techniques in knee reconstruction have inevitably introduced subtle variations in surgical approaches. These variations often emerge due to individual surgeon preferences, their unique expertise, and comfort levels with specific techniques. Anterior knee pain, however, remains a frequent postoperative complication, likely attributed to the extensive and complex innervation of the patella. To address this challenge, some surgeons have adopted patellar denervation, hypothesizing that by reducing nerve signaling from the patellar region, patients may experience a measurable decrease in pain. Methods: A systematic search was performed to include eight recent level I studies to analyze this issue. Results: Of the eight reviews, there were four strong studies that concluded patellar denervation helps decrease anterior knee pain in the acute period, but this may not last long term. The other four papers did not show a difference in anterior knee pain after denervation. Conclusions: This review synthesizes and critically analyzes the current body of literature, aiming to provide clinicians with evidence-based insights into the potential benefits and limitations of incorporating patellar denervation into their surgical especially during the acute post-operative period.

Characteristics of Temporomandibular Joint Osteoarthritis Patients With Condylar Erosion: A Retrospective Cross-Sectional Study.

Condylar erosion (CE) may indicate an active progressive stage of temporomandibular joint osteoarthritis (TMJOA), but no studies have analysed the characteristics of this population. This cross-sectional study analysed the characteristics of TMJOA patients with CE. A total of 267 patients were included. The severity of CE of all joints was evaluated using cone beam computed tomography (CBCT) and scored using a four-point rating scale (0-III). Patients were categorised into mild (grade I), moderate (grade II) and severe (grade III) groups. Demographic and clinical characteristics were summarised and stratified by age and erosion severity. Univariate and multivariate logistic regression analyses were performed based on the assignment of the variables. The proportion of patients under 30 years old is much higher than other age groups. Compared to adults (≥ 20 years old), a higher proportion of adolescent patients (10-19 years old) choose orthodontics department for their first consultation (p < 0.01). And adolescent patients have a higher proportion of temporomandibular joint (TMJ) noise (p < 0.05) and a lower proportion of arthralgia (p < 0.001). Significant differences exist in CE severity between adolescents and adults (p < 0.001). The severe group had the youngest patients (p < 0.05) and the highest proportion of mandibular deviation and abnormal postural habits. Patients under 30 years of age constitute a significant proportion of TMJOA cases with CE. Compared to adults, adolescent patients have more severe CE and less arthralgia. Due to obvious dental and maxillofacial deformities and milder TMJ symptoms, adolescent patients may not be aware that they have TMJ disease, potentially leading to delayed treatment.

PREVALENCE OF DEPRESSION AND ITS IMPACT ON QUALITY OF SLEEP AMONG VARIOUS STAGES OF KNEE OSTEOARTHRITIS

Background: Knee osteoarthritis (OA) is a degenerative disease characterized by chronic pain and impaired mobility, which contribute significantly to psychological distress and poor sleep quality, elevating the overall disease burden. Objective: This study aims to determine the frequency of depression across different stages of knee OA and to evaluate its impact on sleep quality. Methods: Data were collected from 184 participants aged 45 to 70 years using non-probability convenience sampling. Depression was assessed using the Center for Epidemiologic Studies Depression Scale, sleep quality was measured with the Pittsburgh Sleep Quality Index, and knee OA severity was graded using the Kellgren and Lawrence system. The sample consisted of 110 males (59.8%) and 74 females (40.2%). Results: Of the total participants, 49.5% (n=91) showed no signs of depression. Mild depression symptoms were observed in 14.7% (n=27), moderate symptoms in another 14.7% (n=27), and severe symptoms were found in 21.2% (n=39). Sleep quality analysis revealed that while 52.2% reported good sleep quality, 22.8% had poor sleep, and 25% experienced severe disturbances. Conclusion: The study underscores a clear correlation between the severity of knee OA and the incidence of depression, which significantly affects sleep quality. Addressing mental health issues in these patients could improve sleep and overall well-being.

Total Knee Arthroplasty in Patients With Ankle Osteoarthritis Affects Contralateral Ankle Alignment and Postoperative Outcome of Total Knee Arthroplasty.

This study investigated the impact of total knee arthroplasty (TKA) on the alignment of the ankle joint, focusing on changes in coronal alignment of both ankles. This retrospective study, conducted at our hospital, included 64 patients older than 70 years who underwent TKA for varus knee osteoarthritis (OA). Using full-length standing radiographs of both lower extremities taken preoperatively and 6 months postoperatively, we assessed ankle OA grading based on the Takakura-Tanaka classification and measured mechanical hip-knee-ankle (mHKA) and the tibiotalar angle (TTA) on both the surgical and contralateral side. Additionally, we examined the impact of ankle OA on postoperative clinical scores, the Knee injury and Osteoarthritis Outcome Score, following TKA. Based on the classification, ankle OA stage 2 or higher was present in 13 cases on the surgical side and 13 cases on the contralateral side. On the surgical side, mHKA changed from 12.2 to 1.8 degrees varus (P < .001) and TTA from 1.7 to 1.0 degrees varus (P = .002). On the contralateral side, mHKA changed from 4.0 to 5.4 degrees varus (P = .04), and TTA from 2.7 to 3.0 degrees varus (P < .001). In ankle OA stage 2 or higher patients, contralateral TTA changed from 5.2 to 6.5 degrees varus (P < .001) and unchanged in stage 1 patients. Ankle OA stage 2 or higher patients had worse ADL outcomes than stage 1 patients (score: 67.2 and 78.3, respectively, P = .03). This study suggests an apparent interrelationship between knee and ankle OA and the potential negative influence of TKA on ankle OA.

Understanding the role of machine learning in predicting progression of osteoarthritis.

Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures. Out of 1,160 studies initially identified, 39 were included. Most studies (85%) were published between 2020 and 2024, with 82% using publicly available datasets, primarily the Osteoarthritis Initiative. ML methods were predominantly supervised, with significant variability in the definitions of OA progression: most studies focused on structural changes (59%), while fewer addressed pain progression or both. Deep learning was used in 44% of studies, while automated ML was used in 5%. There was a lack of standardization in evaluation metrics and limited external validation. Interpretability was explored in 54% of studies, primarily using SHapley Additive exPlanations. Our systematic review demonstrates the feasibility of ML models in predicting OA progression, but also uncovers critical limitations that currently restrict their clinical applicability. Future priorities should include diversifying data sources, standardizing outcome measures, enforcing rigorous validation, and integrating more sophisticated algorithms. This paradigm shift from predictive modelling to actionable clinical tools has the potential to transform patient care and disease management in orthopaedic practice.

Chondrocyte autophagy mechanism and therapeutic prospects in osteoarthritis.

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.

Clinical and instrumental characteristics of osteoarthritis in hyperuricemia

Objective: to investigate in a multicentre single-stage study the relationships between hyperuricemia (HU) and clinical, instrumental and laboratory parameters of osteoarthritis (OA).Material and methods. The study included 200 patients aged 40 to 75 years with a definite diagnosis of knee (KN) OA that met ACR criteria, with stage I–III OA by Kellgren–Lawrence. The mean age of the patients was 55.9±10.3 years and the body mass index (BMI) was 29.4±6.2 kg/m2. An individual chart was completed for each patient, including anthropometric parameters, medical history and clinical examination data, visual analogue scale (VAS) assessment of KN pain, WOMAC, patient's general health assessment (GHA) and information on comorbidities. All patients underwent standard radiography and magnetic resonance imaging (MRI) of the KN (WORMS), dual-energy X-ray absorptiometry of the lumbar spine and femoral neck, and laboratory examination.Results and discussion. HU was diagnosed in 57 (28.5) patients when the serum uric acid (UA) level was above 360 μmol/L. Patients were divided into two groups according to the presence or absence of HU. The age of the patients in the two groups was comparable, but they differed significantly in terms of disease duration, BMI, waist and hip circumference, which were greater in the HU group (p &lt;0.05). Statistically significant differences were also found in the assessment of the severity of OA course: there were higher pain indices according to VAS, WOMAC total score and its components (pain and functional impairment, FI), GHA in the HU group. On MRI, osteitis was more common in the medial aspect of the tibia (odds ratio 5.75; 95% confidence interval 1.29–25.6; p=0.03). Patients with HU had higher concentrations of CRP, COMP, leptin, insulin, triglycerides and creatinine (p &lt;0.05 for all values).Spearman correlation analysis confirmed the association between HU and duration and radiological stage of OA, the presence of osteitis in the medial aspect of tibia detected by MRI, pain according to VAS and WOMAC, FI according to WOMAC and GHA (p&lt;0.05).Conclusion. At high UA levels, pain values according to VAS and WOMAC are higher, GHA is worse, and CRP and COMP levels are elevated. MRI shows more frequent osteitis in the medial aspect of the tibia in patients with HU. Deciphering the mechanisms that determine the relationship between HU and OA is important for the development of new methods for the prevention and treatment of these diseases.

Sonographic Verification and Clinical Significance of the Features of Surrounding Structures in Knee Osteoarthritis

Background: Osteoarthritis (OA) of the knee joint is one of the most dangerous diseases, the most significant manifestation of which is chronic pain syndrome. There is a low correlation between the radiographic stage of OA and pain progression. First of all, this is a variety of pain syndromes, among which is the pathology of periarticular structures (AS). To date, the contribution of this type to the clinical picture of OA has been sufficiently studied, primarily due to the fact that the list and frequency of these lesions have not yet been described.Aim: to describe the basis of the main periarticular structures in patients with different radiographic stages of knee OA according to ultrasound data.Materials and methods: The observational study has currently included 88 patients who had an outpatient appointment with a rheumatologist for knee osteoarthritis between 2021 and 2023. The study assessed 110 knee joints using clinical and ultrasound techniques.Results: The most common periarticular ultrasound changes, regardless of radiographic stage, were pes anserine tendinopathy (57.3 %), Baker’s cyst (45.5 %), fibrosis of the severe Hoffa body (40 %) and ligamentopathy of the medial collateral ligament (36). ,4). %). A significant correlation was found between the number of changes according to ultrasound and the radiological stage (ρ=0.45 [95 % CI: 0.28, 0.59], p &lt;0.001) as well as between the VAS and the definition of identified ultrasound changes (ρ= 0.29 [95 % CI: 0.11, p=0.002); In addition, it was shown that late stages of OA are associated with a greater content of changes (p &lt;0.001).Conclusion: Changes in periarticular structures are present in most patients with knee osteoarthritis; their number correlates with the VAS value and radiographic stage of OA. Details of these changes, their clinical significance and pathogenetic contribution to the progression of knee OA require further study.

Efficacy of intra-articular injection of combined platelet-rich-plasma (PRP) and hyaluronic acid (HA) in knee degenerative joint disease: a prospective, randomized, double-blind clinical trial.

Intra-articular injections of hyaluronic acid (HA) and platelet-rich plasma (PRP) represent promising options in the conservative treatment of early stages of knee osteoarthritis (OA). Although the combined use of these two compounds seems to have a synergistic effect in pre-clinical studies, few clinical trials compared the association of PRP and HA with PRP and HA alone. The aim of study is toevaluate the efficacy of combined intra-articular injections of PRP and HA in the treatment of mild to moderate knee OA, compared to PRP and HA alone. One hundred and seventy-four patients were prospectively enrolled and randomized to undergo three intra-articular injections of either HA or PRP or the combination of PRP and HA with a two-week interval period. Patients were evaluated before treatment and after 3, 6, and 12months using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee subjective score, Visual Analogue Scale and TEGNER Activity Scores. All the treatments proved to be effective in reducing pain and improving joint function. The analysis of covariance did not show statistically significant differences among the three groups for any of the investigated outcome parameters after 6 and 12months (WOMAC: p = 0.45 and p = 0.64, respectively). No significant differences were found in terms of adverse events (p = 0.49) and painkiller use (p = 0.28 and p = 0.56, respectively) among the three groups. This multicenter, prospective, randomized, double-blind controlled trial revealed that intra-articular injections of PRP + HA, PRP, or HA represent a safe and viable treatment with comparable efficacy in terms of pain relief and functional outcomes in mild to moderate knee OA.

The Role of Serum Level of Col2a1 and Hyaluoronic Acid in Diagnosis of Knee Osteoarthritis

Osteoarthritis (OA) is a complex condition in which affected tissues experience changes in metabolism, structure, biochemistry, and function. This condition arises when chondrocytes fail to balance the synthesis and degradation of extracellular components like proteoglycans and collagens, leading to inflammation of the synovial membrane and joint capsule. Aim of the study: This study was designed to evaluate the serum levels of Type II Collagen alpha 1 (coll2a1) and Hyaluronic Acid (HA) in diagnosis of early stage of knee osteoarthritis in Iraqi patients Subjects and Methods: This case- control study was carried out at Department of Biochemistry, College of Medicine, University of Baghdad and at Rheumatology Department , Baghdad Hospital / Medical City, during the period from September 2022 to March 2023. It included ninety volunteer males and females subdivided into subgroups: Group 1consisted of 50 patients who have had early stages of knee osteoarthritis (KOA) and group 2 involved 40 apparently healthy subjects who served as control group. The diagnosis of KOA was made by a consultant rheumatologist using American College of Rheumatology (ACR) criteria. Moreover, patients were sub- classified according to their BMI (normal weight, overweight and obese) and KOA severity (grad1 and grad 2). Investigations included serum measurements of Human serum coll2a1( type II collagen alpha I) and Human serum HA (Hyaluronic Acid) in all patients and controls by ELISA technique. Results: The mean (±SD) values of Coll2a1, HA, of KOA patients were significantly higher than those of controls (for all, p &lt;0.01). There was significant positive correlation between. The mean value of serum hyaluronic acid was significantly increased in grad 2 KOA when compared with grad 1 KOA patients (p &lt; 0.004). The results found that fibulin-3 has the highest receiver operator characteristic (ROC) and area under curve (AUC=89.2% ) at cutoff (7.50 ng/ml) with sensitivity 80.0 and specificity 80.0 in diagnosis of KOA. Also, serum Coll2a1 has high diagnostic utility (AUC=88.6%) at cutoff (286.00 pg/ml) with sensitivity 82.0 and specificity 80.0 . Conclusion: Assessing non-invasive serum levels of coll2a1 (with a cutoff of 286.00 pg/ml) offers a new biochemical marker for diagnosing the early stages of knee osteoarthritis (KOA) potentially before changes become visible on X-rays. Additionally, measuring serum hyaluronic acid levels could serve as an indicator of disease severity, helping to differentiate between various grades of KOA.

Intraoperative cartilage analysis of the first carpometacarpal joint - comparison with conventional staging according to Eaton and Littler

IntroductionOsteoarthritis of the first carpometacarpal joint is a common pathology of the hand, which may show an increasing prevalence in Germany due to the demographic development. In recent years, not only the current gold standard - the resection arthroplasty of the thumb saddle joint - has been used, but also therapeutic thumb saddle joint arthroscopy. In addition to the patient’s clinical complaints, radiographic diagnostics have been used to decide on treatment, although it has not been proven whether there is a correlation between imaging and clinical complaints.Materials and methodsBetween 2020 and 2022, 20 articular surfaces of the thumb saddle joint undergoing resection arthroplasty for symptomatic basal thumb osteoarthritis were prospectively examined, mapped and compared with preoperative conventional radiographs.ResultsThe evaluation of the corresponding articular surfaces showed a higher cartilage destruction at the articular surfaces of the trapezium compared to the first metacarpal. No correlation was found between the stage of osteoarthritis and the Eaton-Littler classification.ConclusionsOverall, there is a patient-specific heterogeneity of the cartilage damage of the articular surface of the trapezium bone, as well in the metacarpal bone I base in relation to the radiographic diagnosis. Furthermore, an inhomogeneity of the radiographic stage of osteoarthritis of the carpometacarpal joint according to Eaton and Littler in relation to the intraoperatively assessed cartilage damage. The statistical significance of the surgically assessed cartilage damage in relation to the conventional radiographs could not be demonstrated. Thus, the treatment of symptomatic osteoarthritis of the carpometacarpal joint should primarily address the patient’s individual complaints. The radiographic classification according to Eaton and Littler can be used as an additional factor to decide on the surgical procedure but should not delay the therapeutic treatment.Level of evidenceIII.

Sustained therapeutic effects of self-assembled hyaluronic acid nanoparticles loaded with α-Ketoglutarate in various osteoarthritis stages

Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.

PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis.

The molecular mechanism underlying abnormal osteoclastogenesis triggering subchondral bone remodeling in osteoarthritis (OA) is still unclear. Here, single-cell and bulk transcriptomics sequencing analyses are performed on GEO datasets to identify key molecules and validate them using knee joint tissues from OA patients and rat OA models. It is found that the catalytic subunit of protein phosphatase 2A (PP2Ac) is highly expressed during osteoclastogenesis in the early stage of OA and is correlated with autophagy. Knockdown or inhibition of PP2Ac weakened autophagy during osteoclastogenesis. Furthermore, the ULK1 expression of the downstream genes is significantly increased when PP2Ac is knocked down. PP2Ac-mediated autophagy is dependent on ULK1 phosphorylation activity during osteoclastogenesis, which is associated with enhanced dephosphorylation of ULK1 Ser637 residue regulating at the post-translational level. Additionally, mTORC1 inhibition facilitated the expression level of PP2Ac during osteoclastogenesis. In animal OA models, decreasing the expression of PP2Ac ameliorated early OA progression. The findings suggest that PP2Ac is also a promising therapeutic target in early OA.