Search Results (106)

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: The most commonly diagnosed group of rheumatic diseases in children is juvenile idiopathic arthritis. It is characterized by a chronic inflammatory process that leads to the degradation of the bone and joint system and increased secretion of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6. These cytokines contribute to the dysregulation of adipocytokine metabolism, including adiponectin and leptin, as well as extracellular matrix components, such as tenascin C. While it is known that children with JIA exhibit TNF-α-stimulated degradation of most ECM cartilage components, the effect of TNF-α antagonists, such as etanercept, on these processes has not yet been evaluated. Therefore, the aim of our study was to assess the dynamics of changes in tenascin C, adiponectin, and leptin levels in the blood of children with JIA, both before and during therapy. Methods: The study material consisted of blood samples collected from 66 children of both sexes, including 40 girls and 26 boys diagnosed with juvenile idiopathic arthritis and treated with etanercept, as well as from 40 healthy children (22 girls and 18 boys). The quantitative assessment of adiponectin, leptin, and tenascin C levels was performed using commercial ELISA tests. Results: The conducted study revealed that untreated children with JIA exhibit altered plasma levels of all examined parameters—adiponectin, leptin, and tenascin C. Specifically, there was an increase in adiponectin concentration and a decrease in leptin as well as TNC levels compared to healthy children. The results demonstrated the beneficial effects of the TNF-α antagonist, i.e., etanercept, which not only improved the clinical condition of children with JIA but also positively influenced the metabolism of both adipokines and tenascin C. Conclusions: The obtained results suggest the potential use of adiponectin, leptin, and tenascin C as biochemical markers of the effectiveness of etanercept therapy in inhibiting the progression of degenerative joint changes in children with JIA treated with TNF-α inhibitors. Full article

Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions. Methods: Studies selected (1) involved clinical research investigating genetic factors or biomarkers associated with dementia or osteoporosis, and (2) were published in English in a peer-reviewed journal between July 1993 and March 2025. We searched Medline Ovid, Embase, PsycINFO, the Cochrane Library, the Web of Science databases, Google Scholar, and the reference lists of studies following the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). Results: Twenty-three studies were included in this review. These explored the role of the APOE polymorphism (n = 2) and the APOE4 allele (n = 13), associations between TREM2 mutation and late onset AD (n = 1), and associations between amyloid beta and bone remodeling (n = 1); bone-related biomarkers like DKK1, OPG, and TRAIL as predictors of cognitive change (n = 2); extracellular vesicles as bone–brain communication pathways (1); and the role of dementia-related genes (n = 1), AD-related CSF biomarkers (n = 1), and parathyroid hormone (PTH) (n = 1) in osteoporosis–dementia pathophysiology. Conclusions: Bone-related biomarkers active in the Wnt/β-Catenin pathway (Dkk1 and sclerostin) and the RANKL/RANK/OPG pathway (OPG/TRAIL ratio) present consistent evidence of involvement in AD and osteoporosis development. Reports proposing APOE4 as a causal genetic link for both osteoporosis and AD in women are not corroborated by newer observational studies. The role of Aβ toxicity in osteoporosis development is unverified in a large clinical study. Full article

Background: Chronic low back pain (CLBP) is the leading cause of disability both within the United States and globally. However, reliable diagnosis and treatment remains limited due to a lack of objective and image-based biomarkers. Modic changes (MCs) are visible vertebral endplate and bone marrow changes in signal intensity seen on MRI. MCs have emerged as promising correlates with degenerative disc disease and CLBP. Methods: This is a non-systematic literature review. Results: This review synthesizes current evidence on the classification, pathophysiology, and imaging of MCs, with a particular focus on their associations with patient-reported outcomes, including pain (Visual Analog Scale), functional status (Oswestry disability index and Roland-Morris Disability Questionnaire), and health-related quality of life (Short Form-36 and EuroQol 5-Dimension 5 Level). MC type 1 and 2 show significant correlations with symptom severity and predict positive response to basi-vertebral nerve (BVN) ablation, a minimally invasive intervention inhibiting the nerves’ ability to transmit pain signals. Conclusions: Across multiple trials, BVN ablation has shown significant sustained improvements in patient-reported outcomes among patients with MC, reinforcing their role as both a diagnostic and therapeutic biomarker. Full article

Background/Objectives: Degenerative joint diseases (DJDs) involve intricate molecular disruptions within bone, cartilage, and synovial tissues, often preceding overt radiographic changes. These tissues exhibit complex biomolecular architectures and their degeneration leads to microstructural disorganization and inflammation that are challenging to detect with conventional imaging techniques. This review aims to synthesize recent advances in imaging, computational modeling, and sequencing technologies that enable high-resolution, non-invasive characterization of joint tissue health. Methods: We examined advanced modalities including high-resolution MRI (e.g., T1ρ, sodium MRI), quantitative and dual-energy CT (qCT, DECT), and ultrasound elastography, integrating them with radiomics, deep learning, and multi-scale modeling approaches. We also evaluated RNA-seq, spatial transcriptomics, and mass spectrometry-based proteomics for omics-guided imaging biomarker discovery. Results: Emerging technologies now permit detailed visualization of proteoglycan content, collagen integrity, mineralization patterns, and inflammatory microenvironments. Computational frameworks ranging from convolutional neural networks to finite element and agent-based models enhance diagnostic granularity. Multi-omics integration links imaging phenotypes to gene and protein expression, enabling predictive modeling of tissue remodeling, risk stratification, and personalized therapy planning. Conclusions: The convergence of imaging, AI, and molecular profiling is transforming musculoskeletal diagnostics. These synergistic platforms enable early detection, multi-parametric tissue assessment, and targeted intervention. Widespread clinical integration requires robust data infrastructure, regulatory compliance, and physician education, but offers a pathway toward precision musculoskeletal care. 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: The most common limb-salvage procedure for end-stage ankle arthropathy with severe bone defect is arthrodesis. Successful fusion requires rigid metal fixation, effective filling of the bone defect space, and maximal securing of the contact area between the tibia and talus. In cases with severe bone defect, sufficient grafting using autogenous bone alone is limited, and there is still controversy regarding the effectiveness of allogeneic or xenogeneic bone grafting. This study aimed to evaluate the intermediate-term clinical outcomes after shortening arthrodesis using fibular osteotomy for ankle arthropathy with severe bone defect. Methods: Twenty-two patients with shortening ankle arthrodesis were followed up ≥ 3 years. All operations were performed by one senior surgeon and consisted of internal fixation with anterior fusion plate, fibular osteotomy, and autogenous bone grafting. The causes of ankle joint destruction were failed total ankle arthroplasty (7 cases), neglected ankle fracture (6 cases), delayed diagnosis of degenerative arthritis (5 cases), avascular necrosis of talus (2 cases), and diabetic neuroarthropathy (2 cases). Clinical outcomes including daily living and sport activities were evaluated with the Foot and Ankle Outcome Score (FAOS) and the Foot and Ankle Ability Measure (FAAM). Radiological evaluation included fusion rate, time to fusion, leg length discrepancy, and degenerative change in adjacent joints. Results: The FAOS and FAAM scores significantly improved from a mean of 21.8 and 23.5 points preoperatively to 82.2 and 83.4 points at final follow-up, respectively (p < 0.001). Visual analogue scale for pain during walking significantly improved from a mean of 7.7 points preoperatively to 1.4 points at final follow-up (p < 0.001). The average time to complete fusion was 16.2 weeks, and was achieved in all patients. The average difference in leg length compared to the contralateral side was 11.5 mm based on physical examination, and 13.8 mm based on radiological examination. During the average follow-up of 56.2 months, no additional surgery was required due to progression of degenerative arthritis in the adjacent joints, and no cases required the use of height-increasing insoles in daily life. Conclusions: Shortening ankle arthrodesis using fibular osteotomy and anterior fusion plate demonstrated satisfactory intermediate-term clinical outcomes and excellent fusion rate. Advantages of this procedure included rigid fixation, preservation of the subtalar joint, effective filling of the bone defect space, and maximal securing of the contact area for fusion. The leg length discrepancy, which was concerned to be a main shortage, resulted in no significant clinical symptoms or discomfort in most patients. 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

Osteoarthritis (OA) is a degenerative disease of joint tissue characterized by the breaking down of cartilage and resulting changes in synovium and bone. Mechanics and biology interact in a feed-forward manner in that imbalanced joint loading leads to tissue degeneration and vice versa. Amid numerous genetic factors, the Secretory Leukocyte Protease Inhibitor (SLPI) gene encodes a protein that plays a crucial role in inhibiting proteases, modulating inflammation, promoting tissue repair, and regulating immune responses. In the context of OA, SLPI has been identified as a key regulator in joint homeostasis. The release of SLPI in human tissues is augmented by pro-inflammatory factors. Such factors include cytokines released during infection or inflammatory processes, such as interleukins-1 and 6 (IL-1 and IL-6), and tumor necrosis factor alpha (TNF-α) released in many inflammatory rheumatic diseases. In this work, a comprehensive review of SLPI-mediated inflammation in OA, its biological functions, and its association with OA is described, providing a foundation for future investigations into its potential therapeutic use. As there is no effective strategy to treat or prevent OA in clinic, further investigation is encouraged to explore the translational possibility of SLPI for drug development. Full article

Articular cartilage (AC) plays an important role in the biomechanics of synovial joints. Its task is to enable smooth movement and transfer of mechanical loads with minimised friction. AC is characterised by unique mechanical properties resulting from its complex structure, in which the dominant components are type II collagen, proteoglycans and water. Healthy articular cartilage shows elasticity in compression, viscoelastic properties, and the ability to relax stresses under the influence of cyclic loads. In response to different loading modes, it shows anisotropic and non-uniform behaviour, which translates into its cushioning and protective function for the subchondral bone. Significant changes occur in the structure and mechanical properties of cartilage with age as a result of mechanical overload or degenerative diseases, such as osteoarthritis. This results in a deterioration of the cushioning and mechanical function, which leads to progressive degradation of joint tissues. Understanding the mechanical properties of AC is crucial for developing effective diagnostic methods. Analysis of changes in mechanical properties contributes to the early detection of pathological changes. The aim of this paper is to review the current state of knowledge regarding the structure and biomechanical properties of articular cartilage, and to analyse conventional and alternative diagnostic methods in the context of their suitability for assessing the state of AC, particularly in the early stages of degenerative processes. Full article

Osteoarthritis (OA) is the most prevalent degenerative joint disorder worldwide, causing significant declines in quality of life. The osteochondral junction (OCJ), a critical structural interface between deep cartilage and subchondral bone, plays an essential role in OA progression but is challenging to assess using conventional magnetic resonance imaging (MRI) due to its short T2 relaxation times. This study aimed to evaluate the utility of ultrashort echo time (UTE) MRI biomarkers, including macromolecular fraction (MMF), magnetization transfer ratio (MTR), and T2*, for in vivo quantification of OCJ changes in knee OA for the first time. Forty-five patients (mean age: 53.8 ± 17.0 years, 50% female) were imaged using 3D UTE-MRI sequences on a 3T clinical MRI scanner. Patients were stratified into two OA groups based on radiographic Kellgren–Lawrence (KL) scores: normal/subtle (KL = 0–1) (n = 21) and mild to moderate (KL = 2–3) (n = 24). Quantitative analysis revealed significantly lower MMF (15.8  ±  1.4% vs. 13.6 ± 1.2%, p < 0.001) and MTR (42.5 ± 2.5% vs. 38.2  ±  2.3%, p < 0.001) in the higher KL 2–3 group, alongside a higher trend in T2* values (19.7  ±  2.6 ms vs. 21.6  ±  3.8 ms, p = 0.06). Moreover, MMF and MTR were significantly negatively correlated with KL grades (r = −0.66 and −0.59; p < 0.001, respectively), while T2* showed a weaker positive correlation (r = 0.26, p = 0.08). Receiver operating characteristic (ROC) analysis demonstrated superior diagnostic accuracy for MMF (AUC = 0.88) and MTR (AUC = 0.86) compared to T2* (AUC = 0.64). These findings highlight UTE-MT techniques (i.e., MMF and MTR) as promising imaging tools for detecting OCJ degeneration in knee OA, with potential implications for earlier and more accurate diagnosis and disease monitoring. Full article

Degenerative joint disease remains a leading cause of global disability, with early diagnosis posing a significant clinical challenge due to its gradual onset and symptom overlap with other musculoskeletal disorders. This review focuses on emerging diagnostic strategies by synthesizing evidence specifically from studies that integrate biochemical biomarkers, advanced imaging techniques, and machine learning models relevant to osteoarthritis. We evaluate the diagnostic utility of cartilage degradation markers (e.g., CTX-II, COMP), inflammatory cytokines (e.g., IL-1β, TNF-α), and synovial fluid microRNA profiles, and how they correlate with quantitative imaging readouts from T2-mapping MRI, ultrasound elastography, and dual-energy CT. Furthermore, we highlight recent developments in radiomics and AI-driven image interpretation to assess joint space narrowing, osteophyte formation, and subchondral bone changes with high fidelity. The integration of these datasets using multimodal learning approaches offers novel diagnostic phenotypes that stratify patients by disease stage and risk of progression. Finally, we explore the implementation of these tools in point-of-care diagnostics, including portable imaging devices and rapid biomarker assays, particularly in aging and underserved populations. By presenting a unified diagnostic pipeline, this article advances the future of early detection and personalized monitoring in joint degeneration. Full article

Background: Triangular fibrocartilage complex (TFCC) tears are a common source of ulnar-sided wrist pain. Surgery has to be performed in case of instability, pain, or if non-operative treatment fails. Overall, the results are very good. However, some patients still suffer from pain after surgery. Post-operative MR imaging can reveal potential pathologies but it needs to be assessed whether depicted changes are normal or whether these findings have a clinical significance. Therefore, the purpose of this study was to evaluate postoperative MR imaging and the function of the patients’ wrists in order to assess which postoperative changes are correlated with pain. Patients and Methods: All patients with a TFCC lesion who were treated arthroscopically at our hospital between January 2012 and December 2016 were retrospectively enrolled. Seventeen patients with complete data sets were enrolled. Post-operative MRI examinations needed to be performed within 24 months after arthroscopy. The mean magnet resonance imaging (MRI) follow-up was 22 months. The average clinical follow-up was 27.3 months. Age, gender, pain level, PROM scores (Munich Wrist Questionnaire, MWQ), follow-up interval, and TFCC classification (Palmer) were documented. The patients underwent a clinical examination and MR imaging. Results: Ten patients (59%) had scar tissue at the triangular fibrocartilaginous complex (TFCC) and nine (53%) had an effusion in the ulnar recess. These findings were not necessarily associated with pain, as six patients without pain and four with pain had scar tissue at the TFCC and six patients without pain and three with pain showed an effusion in the ulnar recessus. Bone marrow edema could be found in the lunate of five patients (29%) (three with pain, two without pain) and in the distal radial ulnar joint (DRUJ) of one patient (6%) with pain. However, typical degenerative changes were not necessarily associated with pain. Conclusions: This present study is the first study correlating postoperative MRI findings after arthroscopic assisted TFCC surgery with both pain and function. Bone edema seems to be associated with pain, whereas scarring at the TFCC is visible on MRI but is not necessarily associated with pain. Full article

Objectives: Osteoarthritis (OA) is a prevalent chronic degenerative joint disorder marked by cartilage degradation, subchondral bone remodeling, and synovial inflammation. Despite its widespread occurrence, effective pharmacological interventions to halt or reverse OA progression remain elusive. Thus, an in-depth understanding of its pathogenesis is imperative for developing novel therapeutic strategies. Methods: Sixty-four male Sprague-Dawley rats (8 weeks old, weighing 180–220 g) were randomly assigned to two groups: the anterior cruciate ligament transection (ACLT) group and the sham-operated group. Primary osteoblasts were isolated from the subchondral bone at 0, 4, 8, and 12 weeks after ACLT. Nuclear magnetic resonance (NMR)-based metabolomics was used to elucidate metabolic changes and the underlying mechanisms in osteoblasts. Results: A total of 26 metabolites were identified from the NMR spectra of osteoblasts. Distinct metabolic profiles were observed in the ACLT group at 0, 4, 8, and 12 weeks after surgery. In particular, several differential metabolites were identified, including glucose, lactate, NADP⁺, phosphocreatine, and alanine, as well as eight perturbed pathways, such as alanine, aspartate, and glutamate metabolism, phenylalanine metabolism, and taurine metabolism. Conclusions: Key energy-related metabolites, including glucose, lactate, creatine phosphate, and creatine, were identified as key markers of osteoblast dysfunction in OA, underscoring the profound metabolic perturbations induced by ACL injury. These disturbances in energy homeostasis are strongly implicated in the progression of OA. In addition, branched-chain amino acids emerged as potential biomarkers, further highlighting the metabolic dysregulation associated with the disease. Taken together, the metabolic changes observed in rat osteoblasts following ACL injury reveal a complex interplay between energy and amino acid metabolism, providing critical insights into the pathogenesis of post-traumatic OA and highlighting potential therapeutic targets. Full article

Osteoarthritis (OA) is a chronically progressive degenerative arthropathy characterized by the loss of cartilage, changes in subchondral architecture, and ongoing inflammation resulting in reduced mobility and pain. This study assessed the treatment potential of a combination of chondroitin and glucosamine enriched with Curcumin C3 Complex (C3GC) in modulating the pathophysiological features in mouse models with surgically induced OA and in dogs with naturally occurring OA. A cohort of 24 male C57BL/6 mice aged 3 months old were surgically destabilized with medial meniscus (DMM) to cause osteoarthritis. These animals underwent a nutritional intervention with C3GC or with GC over a course of 8 weeks. In order to evaluate cartilage health and subchondral bone structure, we carried out a combination of behavioral tests, micro-computed tomography (micro-CT), and histopathological examinations. In addition, a cohort of 12 OA-diagnosed retired police dogs were administered C3GC supplements or conventional care over a course of 30 days, with pain measurement and serum concentrations of MMP-3 and TNF-α determined before and after treatment. According to our findings, the administration of C3GC was determined to preserve subchondral microarchitectural structure integrity (p < 0.05) and resulted in better motor function in comparison with GC. In animals taking nutritional supplements, the OARSI scores of joint tissue sections were reduced, with the medial tibial plateau OARSI score being particularly low in the C3GC group (p < 0.0001). In dogs, treatment with C3GC resulted in a 24.5% reduction in serum MMP-3 levels (p < 0.01), and there was also a 20.8% decrease in serum TNF-α levels (p < 0.05), along with a decrease in subjective pain assessment. The results are in support of the chondroprotective, anti-inflammatory, and analgesic properties of C3GC and justify future research on the potential utility of C3GC in treating osteoarthritis. Full article