Search Results (299)

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3⁺ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3⁺/CD44⁺ cells in femoral and tibial cartilage and meniscus. Ki67⁺ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44⁺. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA. Full article

Background/Objectives: Osteoarthritis (OA) is a progressive joint disease characterized by inflammation, cartilage degradation, and subchondral bone changes, for which effective disease-modifying therapies are lacking. Messenger RNA (mRNA)-based therapeutics offer a versatile approach to modulate joint pathology, but their application to OA remains limited. Methods: We evaluated intra-articular delivery of therapeutic mRNAs using polyplex nanomicelles, a non-inflammatory and minimally invasive carrier system, in a rat model of inflammation-driven OA induced by monosodium iodoacetate (MIA). Results: IL-1 receptor antagonist (IL-1Ra) mRNA reduced synovial inflammation and alleviated pain and swelling. RUNX1 mRNA, a transcription factor critical for chondrogenesis, supported chondrocyte viability, type II collagen expression, and cartilage structure. Under conditions of pronounced inflammation, however, the protective effects of RUNX1 mRNA alone were modest. Notably, combined administration of IL-1Ra and RUNX1 mRNAs produced synergistic therapeutic benefits, with enhanced chondroprotection and preservation of subchondral bone integrity. Conclusions: These findings suggest that while RUNX1 is essential for maintaining cartilage homeostasis, effective control of joint inflammation is required for its therapeutic activity. Dual mRNA therapy delivered by polyplex nanomicelles therefore represents a promising strategy to address the multifactorial pathology of OA. Full article

Osteoarthritis (OA) is an inflammatory disorder characterized by metabolic changes in the bone tissue, including the degeneration of hyaline cartilage (articular cartilage) and fibrocartilage (including the meniscus and labrum), sclerosis of the subchondral bone, and osteophyte formation. OA poses a major challenge for adults of all ages, leading to increased morbidity and decreased quality of life. The current conventional therapies mainly focus on pain control, with no definitive or regenerative therapies to reverse OA progression available. Lasers consist of electromagnetic waves generated by radiation emitted by an excited material. In medicine and dentistry, photobiomodulation by low-power laser therapy (photobiomodulation therapy [PBMT]) has been widely applied clinically to promote healing, regenerate tissue, modulate inflammation, and relieve pain. Basic studies have explored the regulation of OA manifestations and joint inflammation using PBMT, as well as the mechanisms of action involved, and clinical research has validated the beneficial effects of PBMT for patients with OA. However, the effects of PBM on OA and its mechanisms of action remain unknown. Herein, we review basic research that has examined the effects of PBMT on OA using in vitro and in vivo testing and discuss future challenges and prospects. Full article

Background/Objectives: Osteoarthritis is a slowly evolving joint disorder defined by cartilage degradation, synovial inflammation, subchondral bone hardening, and the growth of osteophytes. Increasing evidence highlights the role of metabolic factors in osteoarthritis onset and progression. This study investigated the link between metabolic syndrome and the level of knee impairment in postmenopausal respondents suffering from knee osteoarthritis. Methods: A total of 200 participants aged 60–75 years with knee pain were enrolled in this observational cross-sectional study conducted between 2022 and 2023. The case group comprised 120 women with radiographically verified knee osteoarthritis (Kellgren–Lawrence grades II–IV), while 80 age-matched women without radiographic changes served as controls. Clinical and anthropometric measures, metabolic indicators, and radiographic findings were collected. Functional status was assessed using the Lower Extremity Functional Scale and the Lequesne Index. Results: The groups differed significantly with respect to the presence of metabolic syndrome, diastolic blood pressure, and fasting glucose level (p < 0.05). The metabolic syndrome showed modest but significant associations with radiographic knee damage (effect size 4.7%). After adjusting for smoking status and physical activity level, metabolic syndrome remained significantly associated with radiographic damage (effect sizes: 4.8 and 2.2%, respectively). Participants with osteoarthritis but without metabolic syndrome had better functional knee status compared to those with metabolic syndrome (p < 0.05). Conclusions: In postmenopausal women, metabolic syndrome is independently associated with radiographic knee damage and contributes to poorer functional outcomes in participants with knee osteoarthritis, underscoring its potential role as a modifiable risk factor. Full article

Osteoarthritis (OA) is a multifactorial chronic musculoskeletal disorder characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Conventional diagnostic modalities, including radiographic imaging and symptom-based assessments, primarily detect disease in its later stages, limiting the potential for timely intervention. Inflammatory biomarkers, particularly Interleukin-6 (IL-6), Tumour Necrosis Factor-alpha (TNF-α), and Myeloperoxidase (MPO), have emerged as biologically relevant indicators of disease activity, with potential applications as companion diagnostics in precision medicine. This review examines the diagnostic and prognostic relevance of IL-6, TNF-α, and MPO in OA, focusing on their mechanistic roles in inflammation and joint degeneration, particularly through the activity of fibroblast-like synoviocytes (FLSs). The influence of sample type (serum, plasma, synovial fluid) and analytical performance, including enzyme-linked immunosorbent assay (ELISA), is discussed in the context of biomarker detectability. Advanced statistical and computational methodologies, including rank-based analysis of covariance (ANCOVA), discriminant function analysis (DFA), and Cox proportional hazards modelling, are explored for their capacity to validate biomarker associations, adjust for demographic variability, and stratify patient risk. Further, the utility of synthetic data generation, hierarchical clustering, and dimensionality reduction techniques (e.g., t-distributed stochastic neighbour embedding) in addressing inter-individual variability and enhancing model generalisability is also examined. Collectively, this synthesis supports the integration of biomarker profiling with advanced analytical modelling to improve early OA detection, enable patient-specific classification, and inform the development of targeted therapeutic strategies. Full article

Background: Autologous osteochondral transplantation (AOT)—the transfer of hyaline cartilage with its underlying subchondral bone—is well established for focal osteochondral lesions, yet evidence for larger (>200 mm²) defects is limited. We assessed clinical and functional outcomes of AOT in patients with osteochondral knee lesions exceeding 200 mm². Methods: In this retrospective cohort study, 52 patients underwent AOT for full-thickness osteochondral defects of the femoral condyles or patellofemoral joint. All lesions were ≥200 mm² and treated with a standardized press-fit technique using one to four overlapping cylindrical grafts. Pain and knee function were evaluated preoperatively and at 3, 6, and 12 months postoperatively with the Visual Analogue Scale (VAS), Tegner–Lysholm Knee Score (TLKS), and Knee Society Score (KSS). Results: Mean defect size was 224.4 ± 84.5 mm². The VAS improved from 6.32 ± 1.1 preoperatively to 0.72 ± 0.6 at 12 months (p < 0.001). The TLKS rose from 58.6 ± 11.4 to 95.0 ± 6.8 and the KSS from 63.8 ± 12.2 to 97.4 ± 4.9 during the same period (both p < 0.001). Most gains occurred within the first 3–6 months and were sustained at 12 months. No major surgical complications were observed, and outcomes were unaffected by age, sex, or graft number/size. Conclusions: AOT is a safe, effective option for large osteochondral knee defects (>200 mm²), offering rapid, durable pain relief and excellent functional recovery while preserving native joint structures. Accurate donor site reconstruction and precise graft placement in the weight-bearing zone appear critical for optimal results. Longer-term prospective studies are needed to confirm durability and refine patient-selection criteria. Full article

The objective of the present study was to compare the diagnostic performance of radiography to computed tomography (CT) for the diagnosis of distal tarsal osteoarthritis. All images were interpreted and scored by 2 evaluators until a consensus was reached; they were blinded to the history, final imaging diagnosis, and results of the corresponding radiographic or CT study. On radiographs and CT images of 54 tarsi, 6 criteria (osteophyte/enthesophyte height, small/large subchondral bone radiolucencies, subchondral bone thickness, joint space narrowing) were scored in the proximal intertarsal (PIJ), distal intertarsal (DIJ), and tarsometatarsal joint (TMTJ). Compared to CT, mean radiographic scores were significantly lower for 1. small and large subchondral bone radiolucencies in all joints (p < 0.001–0.03); 2. subchondral bone thickness in the PIJ and DIJ (p = 0.03 and 0.005); and 3. enthesophyte and joint space narrowing score in the DIJ (p = 0.04 and 0.002). Low-to-high positive predictive values (PPV) were calculated for the individual criteria in all joints (0–100%). For the sum of scores of all criteria in the PIJ, DIJ, or TMTJ, respectively, PPVs were high (94–98%). In conclusion, radiography is a useful screening tool provided multiple criteria are assessed. However, CT offers significant advantages for the diagnosis of distal tarsal OA. Full article

Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by the addition of bone morphogenetic protein-2 (BMP-2) or amorphous calcium phosphate granules with strontium ions (Sr-ACP), in order to improve the clinical regeneration of subchondral bone, still incomplete. Methodology: Normal human osteoblasts (NHOsts) were seeded on the scaffolds and grown for 14 days in the presence of human osteoclasts and conditioned medium of human endothelial cells. NHOst adhesion and morphology were observed with transmission electron microscopy, and metabolic activity was tested by Alamar blue assay. The expression of osteoblast- and osteoclast-typical markers was evaluated by RT-PCR on scaffolds modified by enrichment with BPM-2 or Sr-ACP, as well as on unmodified material used as a control. Results: NHOsts adhered well to all types of scaffolds, maintained their typical morphology, and secreted abundant extracellular matrix. On the modified materials, COL1A1, SPARC, SPP1, and BGLAP were more expressed than on the unmodified ones, showing the highest expression in the presence of BMP-2. On Sr-ACP-enriched scaffolds, NHOsts had a lower proliferation rate and a lower expression of RUNX2, SP7, and ALPL compared to the other materials. The modified scaffolds, particularly the one containing Sr-ACP, increased the expression of the osteoclasts’ typical markers and decreased the OPG/RANKL ratio. Both types of scaffold modification were able to increase the osteoinductivity with respect to the original scaffold used in clinical practice. BMP-2 modification seemed to be more slightly oriented to sustain NHOst activity, and Sr-ACP seemed to be more slightly oriented to sustain the osteoclast activity. These could provide a concerted action toward better regeneration of the entire osteochondral unit. Full article

While anatomic total shoulder arthroplasty is a successful procedure that provides reliable pain relief and restoration of function in most patients, its success has been limited by glenoid component loosening. While series reporting the outcomes of inlay glenoid components have demonstrated excellent clinical outcomes with low rates of component loosening and need for revision, surgeons have been hesitant to adopt these implants due to concerns of inadequate pain relief secondary to the remaining glenoid rim contacting the humeral head implant. The inset glenoid component, a variant of the traditional inlay components, has gained interest because its design aims to achieve similar stability to traditional inlay components through implantation within strong subchondral bone, reduce the amount of glenoid vault removed compared to inlay components, and has a glenoid face designed to limit the rocking-horse phenomenon. In limited series, the inset glenoid component has demonstrated superior biomechanical and clinical performance compared to traditional onlay glenoid components. Although there have been minimal clinical studies investigating the inset glenoid in comparison to onlay and inlay components to date, a subset of case series with short-term follow-up have demonstrated favorable outcomes. The purpose of this article was to review the design rationale, biomechanical evidence, and clinical performance of the inset glenoid component. Full article

Sheep have been widely used as a model for osteoporosis research. This study aimed to characterise changes in microstructure and composition in lumbar vertebrae L1–L7 and the proximal femur after implementation of a bone loss induction protocol (in this species). A sham control and experimental group (glucocorticoid-treated ovariectomized sheep) were used (n = 6/group), with a study duration up to the 24th postoperative week. Through micro-computed tomography, vertebrae and femoral head trabecular bones from the experimental group presented a consistent decrease in bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) and an increase in trabecular separation (Tb.Sp) and total porosity (p > 0.05). The mineral density of the femoral heads from the experimental group showed a statistically significant decrease (p ˂ 0.05). The entire histomorphometric analysis of the vertebrae in the experimental group showed an increase in cortical porosity (Ct.Po) and a decrease in cortical thickness (Ct.Th) (p ˂ 0.0001 and p ˂ 0.001, respectively). Vertebrae L6 and L7 were the most affected, showing a significant increase in Ct.Po (p < 0.05) and a significant decrease in Ct.Th at the L6 level (p < 0.05). Regarding the trabecular bone at the vertebral level, only L4 showed a significant increase in Tb.Sp (p ˂ 0.05). In the femoral heads’ subchondral cortical layer, the Ct.Po increased significantly and Ct.Th decreased (p < 0.01), and at the trabecular level, the BV/TV, Tb.Th, and Tb.N decreased significantly, while Tb.Sp increased (p < 0.05). In conclusion, the L4, L6 and L7 vertebrae seem the most suitable for further preclinical and translational studies of vertebral augmentation or spinal fusion in this animal model. Full article

Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management. Full article

Osteochondritis Dissecans (OCD) is a joint condition characterized by damage to the surface of the joint and the underlying subchondral bone, leading to early-onset osteoarthritis. It predominantly affects the knee, elbow, and ankle, with higher prevalence in juveniles actively participating in sports, which complicates the condition due to slow healing processes and prolonged restrictions on physical activities. This review aims to summarize current knowledge on OCD in athletes, with emphasis on sport-specific risk factors, diagnosis, and treatment, to support clinical decision-making and future research. We conducted searches in the PubMed and Embase databases, covering the period from 2014 to 2024. The keywords used in the search covered most common sports in combination with term osteochondritis dissecans. This review examines the impacts of various sports on the development of OCD, analyzing prevalence and risk factors, with a focus on sports-specific risks across athletic disciplines like football, basketball, baseball, and gymnastics. The significance of early detection, intervention, and sport-specific conditioning is underscored to prevent the condition and manage it effectively. Moreover, the review highlights the positive prognosis for athletes, particularly adolescents, recovering from OCD, with a high rate of return to sport. Understanding the sports-specific risks, ensuring early intervention, and adopting a cautious, stepwise return to sport are critical for managing OCD effectively, thereby safeguarding the health and careers of athletes. Full article

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article

This study described, assessed and correlated ultrasonographic, computed tomographic, and histological findings in the sacroiliac joints of adult Warmblood horse cadavers. In total, 25 joints from 15 horses were examined post-mortem using transrectal ultrasonography and helical computed tomography. Findings on computed tomography were graded in the caudal joint third (caudally) and for the entire joint as mild, moderate, or severe. In total, 11 joints from nine horses were evaluated histologically. All joints (100%) showed abnormalities on computed tomography, and 92% (23/25) displayed abnormal ultrasonographic findings. The most common ultrasonographic findings were osteophytes (92%), joint effusion (76%), and sacral/iliac bone modeling (76%). Computed tomography revealed osteophytes (92% caudally, 100% overall), sclerosis (72% caudally, 88% overall), subchondral bone lesions (60% caudally, 88% overall), and enthesophytes (60% caudally, 68% overall). The most severe CT findings occurred caudally (44%), whereas 24% occurred cranially,16% in the mid portion of the SIJ, and 16% were multifocally present in the SIJ Histological analysis showed degenerative changes in the cartilage, subchondral bone, and the joint capsule. Horses with more pronounced imaging abnormalities also showed corresponding histological degeneration. Significant correlations were found between computed tomographic findings caudally and in the entire joint (r_s = 0.915, p < 0.001, n = 25), and between imaging and histological findings (computed tomography: r_s = 0.731, p = 0.011, n = 11; ultrasonography: r_s = 0.67, p = 0.024, n = 11). Non-significant correlations were observed between mean ultrasonographic and computed-tomographic grades (r_s = 0.35, p = 0.087, n = 25). Findings suggest these structural changes may reflect adaptation to joint loading. Transrectal ultrasonography appears suitable as a first-line diagnostic tool. However, future studies are essential to compare the diagnostic imaging findings of SIJs in asymptomatic and symptomatic horses to elucidate their clinical relevance. Full article

Background/Objectives: Osteoarthritis is a degenerative joint disease that affects people worldwide. It is characterized by joint pain, synovial inflammation, and the degradation of articular cartilage with subchondral bone. Presently, there is no known cure, and pharmacological treatment options are limited. Blueberries contain phytochemicals, which have been linked to positive health benefits and may offer therapeutic benefits. Therefore, the purpose of this study was to examine the dose-dependent effects of whole blueberries on arthritis symptoms in a monosodium iodoacetate (MIA)-induced rat model of osteoarthritis. Methods: Forty female rats were used for this study. Thirty were injected with MIA to induce joint degradation associated with osteoarthritis. Ten served as controls without MIA induction. The MIA-induced rats were randomized into three groups. All groups were fed a casein-based diet, with two of the MIA-induced groups receiving an addition of whole-blueberry powder at 5% and 10%. Fasted blood specimens and tissues of interest were collected post-euthanasia for analysis. Mechanical allodynia and joint widths were assessed throughout this study. Results: MIA induction resulted in changes in pain behaviors and the development of mechanical allodynia. The MIA injection produced inflammation, pain symptoms, and behaviors that are representative of those observed in humans with osteoarthritis. The incorporation of whole blueberries into diets reduced pain behaviors and inflammation. Conclusions: Overall, whole blueberries showed limited, non-dose-dependent effects in the MIA-induced rat model of osteoarthritis. While some outcomes improved in blueberry-treated groups, the overall results were not consistently significant. These preliminary findings suggest potential biological activity and support the further investigation of blueberries’ therapeutic efficacy. Full article