Search Results (72)

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling. We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues (p < 0.001) and correlated with advanced T, N, and overall pathological stages (all p < 0.05, tau = 0.18, 0.21, and 0.23, respectively). High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0.05, tau = −0.23), elevated levels in microsatellite stable (MSS) compared to MSI tumors (p < 0.01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)). Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance. Full article

Background and Objectives: Autologous matrix-induced chondrogenesis (AMIC) is an established technique for the treatment of focal cartilage defects of the knee, with well-documented clinical outcomes. However, the biological processes underlying early postoperative cartilage remodeling remain poorly characterized, and the role of synovial fluid biomarkers in this setting is not well defined. This study aimed to assess short-term changes in selected synovial fluid and serum biomarkers of cartilage turnover after AMIC and to examine their associations with clinical outcomes. Materials and Methods: Fifteen patients undergoing AMIC for focal knee chondral or osteochondral defects were prospectively enrolled. Synovial fluid and serum samples were collected intraoperatively and at 6 and 12 weeks postoperatively. Concentrations of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinases-2 (TIMP-2), cartilage oligomeric matrix protein (COMP), and procollagen type II C-terminal propeptide (PIICP) were measured using multiplex flow luminescence immunoassay. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) and Lysholm scores preoperatively and at 6 and 12 months. Results: Both IKDC and Lysholm scores improved significantly during follow-up. Absolute biomarker concentrations in synovial fluid were low and did not change significantly over time. Nevertheless, higher MMP-3 levels, higher COMP concentrations, and a higher MMP-3/TIMP-2 ratio were associated with poorer clinical improvement. Correlations between synovial fluid and serum biomarker levels were generally weak. Total synovial fluid protein increased postoperatively but did not account for the low biomarker concentrations. Conclusions: Early biomarker profiles after AMIC were characterized by low absolute concentrations without significant temporal changes. However, associations of COMP, MMP-3, and the MMP-3/TIMP-2 ratio with clinical outcomes suggest that relative biomarker patterns may reflect early intra-articular remodeling. Synovial fluid analysis may provide more informative insight into local joint biology than serum measurements in this setting. These findings should be interpreted cautiously and require confirmation in larger cohorts. Full article

Background: Cytokine-like receptor family 1 (CRLF1) has been implicated in tumor progression, yet its prognostic function and mechanistic actions in prostate cancer (PCa) remain elusive. Objective: This investigation sought to clarify the functional role, molecular mechanisms, and clinical relevance of CRLF1 in the progression of PCa. Methods: We conducted extensive bioinformatics analyses utilizing the protein interaction networks and the TCGA-PRAD dataset. CRLF1 and cartilage oligomeric matrix protein (COMP) expression were validated in clinical samples by qRT-PCR and Western blot (WB). Functional assessments, including Transwell invasion, flow cytometry, CCK-8, and wound healing, were conducted in vitro. An in vivo xenograft tumor model was used for further validation. Mechanistic investigations involved genetic perturbation (overexpression and inhibition) of CRLF1 and COMP. Results: Compared to benign tissues, the levels of CRLF1 and COMP were markedly elevated in PCa tissues. Bioinformatics assessments illustrated a robust positive relationship between CRLF1 and COMP, suggesting COMP may function as a downstream mediator. In vitro and in vivo investigations illustrated that silencing CRLF1 significantly suppressed PCa cell growth, invasion, and tumor progression, while enhancing apoptosis. Importantly, suppressing COMP counteracted the cancer-promoting effects triggered by CRLF1 overexpression. At the mechanistic level, CRLF1 facilitates tumor progression by modulating COMP to activate the FAK/PI3K/AKT signaling cascade. Conclusions: Our outcomes demonstrate that CRLF1 promotes PCa progression by targeting COMP to stimulate the FAK/PI3K/AKT signaling axis. This newly identified CRLF1/COMP/FAK/PI3K/AKT pathway underscores CRLF1 as a potential biomarker and therapeutic target for PCa. Full article

Background/Objectives: Osteoarthritis is a chronic joint disorder involving the progressive breakdown of articular cartilage, which leads to joint pain and impaired mobility. The present study investigated the effects of curcuminoids phospholipid (CP) on osteoarthritis progression, assessed its cartilage-protective effects, and elucidated the underlying mechanisms. Methods: Male Sprague–Dawley rats were randomly allocated to six experimental groups. One group received an intra-articular saline injection as the normal control (NC), while the remaining five groups were injected with monosodium iodoacetate (MIA) and consisted of an MIA control group (MC), a positive control group treated with celecoxib (PC, 3 mg/kg), and three groups treated with CP (31.25, 62.5, or 125 mg/kg). Results: Compared with the MC group, CP administration significantly improved pain-related behavior, as assessed by weight-bearing measurements. Micro-computed tomography and histological analyses demonstrated that CP administration mitigated subchondral bone erosion and preserved cartilage integrity. Additionally, the CP treatment significantly reduced markers associated with cartilage degradation, including matrix metalloproteinases and cartilage oligomeric matrix proteins; downregulated the expression of matrix-degrading enzymes; and restored aggrecan expression. Serum levels of inflammatory mediators, including nitric oxide; prostaglandin E₂; C-reactive protein; and pro-inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were reduced following CP administration. Furthermore, CP decreased the activation of nuclear factor kappa B (NF-κB) signaling. Conclusions: These findings suggest that CP may be a promising functional agent for osteoarthritis, demonstrating beneficial effects on pain-related outcomes and cartilage integrity, potentially mediated by its anti-inflammatory activity. Full article

Knee osteoarthritis (KOA) is one of the most prevalent chronic joint disorders, with its incidence rising over the past decade due to an increase in risk factors, including age, obesity, metabolic conditions, sedentary behavior, and mechanical stress on the knee joints. We conducted a cross-sectional, two-group comparison including 70 knee-pain patients aged ≥ 44 years: 50 patients meeting clinical and radiological criteria for TKA and 20 patients undergoing knee arthroscopy as controls. All patients underwent clinical assessments, WOMAC scoring, radiography, and 3T knee MRI. Serum interleukin-6 (IL-6), cartilage oligomeric matrix protein (COMP), vitamin D3, calcium, and phosphorus were measured at admission. TKA patients were older and had higher WOMAC scores. WOMAC discriminated groups perfectly (AUC = 1.000), but age discriminated well (AUC = 0.911). IL-6 (AUC = 0.819) and COMP (AUC = 0.838) were significant discriminators, with IL-6 threshold ≥ 4.585 pg/mL achieving 66% sensitivity and 85% specificity and COMP cutoff ≥ 11.52 ng/mL achieving 84% sensitivity and 75% specificity. TKA group vitamin D3 levels were considerably lower but had limited discriminatory performance (AUC = 0.683). Although all patients had adequate mineral metabolism, TKA patients had lower serum calcium and higher serum phosphorus levels than controls. Full article

Osteoarthritis (OA) is the most common multifactorial joint disease characterized by progressive cartilage degradation and impaired tissue repair. Osteochondral defects represent a major clinical challenge within OA, as damage to cartilage and underlying bone can initiate degenerative changes and contribute to joint deterioration. The Wnt/β-catenin signaling pathway plays an important role in OA pathogenesis, and its dysregulation contributes to chondrocyte catabolism and cartilage loss. NOTUM, an extracellular Wnt inhibitor, has emerged as a potential therapeutic modulator capable of restoring signaling balance and promoting cartilage homeostasis. This study aimed to evaluate the efficacy of NOTUM compared with hyaluronic acid (HA), human adipose-derived mesenchymal stromal cells (hAd-MSCs), and Colchicine in a rabbit osteochondral defect model relevant to osteoarthritis. Twenty-seven New Zealand White rabbits underwent standardized femoral condyle injury and received single-dose treatments. Serum levels of cartilage biomarkers—Procollagen Type IIA N-terminal Propeptide (PIIANP) and Cartilage Oligomeric Matrix Protein (COMP)—were measured by ELISA at 4, 6, and 8 weeks post-surgery, and histological repair at week 12 was assessed using the modified O’Driscoll scoring system. NOTUM treatment significantly increased PIIANP and decreased COMP levels compared with HA, indicating enhanced cartilage synthesis and reduced degradation. Histological scores confirmed superior surface morphology and tissue composition in NOTUM-treated joints. These findings suggest that NOTUM performs a protective and regenerative effect through Wnt/β-catenin modulation, supporting the conclusion that it enhances osteochondral defect repair and motivating further studies of NOTUM as an OA therapy. Full article

Background/Objectives: Osteoarthritis (OA) remains a global health problem, as it can cause permanent joint damage, leading to irreversible disability. Therefore, there is a need for accessible and non-invasive alternative examinations, such as USG, serum COMP, and 25-hydroxyvitamin D [25(OH)D] assessment. This study aims to analyze the correlation between serum COMP and 25(OH)D levels and the degree of articular cartilage degradation in patients with knee OA, based on findings from USG and MRI examinations. Methods: A cross-sectional analytical study was conducted at Mohammad Hoesin Hospital, Palembang, from December 2024 to August 2025. 31 patients diagnosed with knee OA based on the 1990 American College of Rheumatology (ACR) classification criteria were enrolled. Serum COMP and 25(OH)D levels were measured. All patients underwent standardized USG and MRI examinations of the knee. Spearman’s rank correlation coefficient was used for statistical analysis. Results: The majority of the study subjects were female, comprising 23 (74.2%). The mean age was 63.90 ± 7.77 years with a body mass index of 25.46 ± 5.51 kg/m². Most subjects were engaged in heavy physical activity 17 (54.8%). Laboratory examination showed serum COMP levels with a median of 869 ng/mL and a range of 136–3302 ng/mL. Meanwhile, the 25(OH)D level demonstrated a mean value of 24.84 ± 7.33 ng/mL. The analysis revealed a strong and statistically significant positive correlation between serum COMP levels and the degree of articular cartilage degradation in knee OA. This correlation was observed in both USG (r = 0.61; p < 0.001) and MRI assessments (r = 0.72; p < 0.001). In contrast, serum 25(OH)D levels showed no significant correlation with cartilage degradation. The correlation coefficient between 25(OH)D levels and USG-assessed cartilage degradation was r = −0.12 (p = 0.51), and for MRI assessment, it was r = 0.17 (p = 0.92). Conclusions: A strong and significant positive correlation exists between serum COMP levels and the degree of articular cartilage degradation based on USG (r = 0.61; p < 0.001) and MRI (r = 0.72; p < 0.001). In contrast, serum 25(OH)D levels showed no significant correlation with cartilage degradation, implying that 25(OH)D may not directly reflect the extent of structural cartilage damage in knee osteoarthritis. This finding proves that an increase in serum COMP levels is associated with an increase in the degree of articular cartilage degradation in knee OA as measured by both USG and MRI. Full article

Surface Plasmon Resonance imaging (SPRi) is a powerful label-free technique for high-throughput biochemical analysis. Wavelength modulation is particularly suitable for SPRi due to its wide dynamic range and robustness to fabrication tolerances. However, conventional systems relying on tunable filters (e.g., AOTF, LCTF) suffer from high cost, complexity, and limited temporal resolution. To overcome these drawbacks, we developed a rapid wavelength-modulation SPRi system using a multi-LED source and an adaptive second-order fitting (ASF) algorithm. The system covers the 730–805 nm spectrum with five LEDs. The ASF algorithm first performs a coarse full-spectrum scan to locate the resonance wavelength, then dynamically selects an optimal three-LED subset for fast second-order fitting, enabling accurate reconstruction of resonance wavelength without mechanical scanning. This approach significantly reduces cost and complexity while achieving a scanning cycle of 105 ms, RI resolution of 5.54 × 10⁻⁶ RIU, dynamic range of 0.0241 RIU, and excellent multi-channel consistency. The system has been successfully applied to monitor multi-channel antibody–antigen interactions in real time. Furthermore, it was used to detect cartilage oligomeric matrix protein (COMP) in synovial fluid, where an elevated concentration in an osteoarthritis sample versus a control aligned with its role as a cartilage catabolism marker. This work validates a practical and reliable platform for early diagnosis of osteoarthritis. Full article

The intracellular retention of misfolded extracellular matrix proteins is a common disease mechanism in various rare skeletal diseases. This discovery has driven the study of ER stress and the unfolded protein response (UPR) as a promising therapeutic target in several skeletal dysplasias. In the case of COL10A1 mutations, targeting the UPR resulted in a clinical trial of the repurposed drug carbamazepine; however, for other closely related skeletal disorders, treatment with carbamazepine was ineffective, indicating the need for suitable markers for in vitro screenings of potential drug treatments. Mutations in cartilage oligomeric matrix protein (COMP), a cartilage structural protein, cause both multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH); together referred to as the COMPopathies, which result from the intracellular retention of mutant COMP to varying degrees. In contrast to other closely related skeletal disorders, caused by mutations in cartilage structural proteins, the involvement of the UPR is less clear, and so far, no common COMPopathy marker has been identified. Here, using cell models of COMPopathies, we identified MMP9 upregulation as a common feature of six pathogenic COMP variants that do not induce a prominent UPR. We further show that the archetypal p.V194D matrilin-3 MED variant (which causes MED) does not induce MMP9 expression, suggesting that MMP9 upregulation could serve as a specific marker of COMPopathies in vitro. Full article

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are rare, autosomal dominant skeletal dysplasias characterised by disproportionate short stature, joint deformities, and early-onset osteoarthritis. These conditions result from mutations in key cartilage extracellular matrix (ECM) components, including cartilage oligomeric matrix protein (COMP), matrilin-3, and type IX collagen. Although genetically and clinically heterogeneous, PSACH and MED share convergent pathogenic mechanisms. Misfolded mutant ECM proteins are retained within the endoplasmic reticulum (ER) of growth plate chondrocytes, triggering chronic ER stress and impairing chondrocyte proliferation, differentiation, and survival. Moreover, some of the mutant protein is secreted and incorporated into the matrix, leading to altered collagen fibrillogenesis, disrupted proteoglycan distribution, and compromised biomechanical integrity. These alterations extend beyond cartilage, impacting tendons, ligaments, and muscle–tendon junctions, contributing to joint laxity, impaired force transmission, and mild myopathy. This review discusses the structural and functional consequences of ECM disorganisation in PSACH and MED, highlighting its central role in disease progression and emphasising the importance of considering ECM abnormalities when developing therapeutic strategies for rare short stature-associated skeletal disorders. Full article

This review covers the roles of cartilage oligomeric matrix protein (COMP), an established biomarker of cartilage breakdown in pathological tissues in osteoarthritis, and in emerging areas in extracellular matrix and vascular remodeling associated with trauma, fibrosis and cancer. COMP is produced by chondrocytes, tenocytes, myofibroblasts, and in some specialized tissue contexts, endothelial and vascular smooth muscle cells. COMP expression by tendon and cartilage cells is sensitive to weight bearing and tensional mechanical stimulation. Vascular smooth muscle cells are sensitive to shear forces which regulate COMP expression in vascular tissues in atherosclerosis and in carotid stenosis. COMP is a multivalent bridging molecule that stabilizes tissues. It facilitates the signaling of TGF-β and BMP-2 in chondrogenesis, osteogenesis, tissue fibrosis, vascular and ECM remodeling and tumor development by providing a multimeric environment through which growth factor binding and receptor activation can occur. Engineered COMP proteins have been used as molecular templates in the development of chimeric therapeutic proteins of potential application in repair biology. Tie2 (Angiopoietin-1 receptor, Tyrosine-protein kinase receptor TEK), when activated by an engineered COMP-inspired angiopoietin-2 pentamer, is a potent angiogenic molecule of obvious application in wound healing. COMP’s multifunctional properties show it is much more than a biomolecular marker protein through its ability to participate in many biological processes. Further studies are warranted to fully explore the biology of this fascinating molecule, particularly in the wound repair processes. Full article

The COVID-19 pandemic has revealed significant secondary complications affecting musculoskeletal (MSK) health, especially in patients with pre-existing conditions. This review synthesizes data from clinical and experimental studies on key MSK biomarkers, including cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), osteocalcin, alkaline phosphatase (ALP), procollagen type I N-terminal peptide (PINP), osteopontin (OPN), matrix metalloproteinases (MMP-3 and MMP-9), myostatin, IGF-1, follistatin, and creatine kinase. COVID-19 is associated with decreased COMP and osteocalcin levels, indicating cartilage degradation and impaired bone formation, alongside elevated HA, ALP, PINP, OPN, and MMPs, reflecting increased joint inflammation, bone remodeling, and tissue breakdown. Changes in myostatin, IGF-1, follistatin, and creatine kinase levels have been shown to be linked with COVID-19-related sarcopenia. These biomarker alterations provide insight into the underlying mechanisms of MSK damage in COVID-19 patients and highlight the potential for using these markers in early diagnosis and management of post-COVID musculoskeletal disorders. Further longitudinal research is essential to develop targeted therapies aimed at mitigating long-term MSK complications in affected individuals. Full article

Background and Objectives: Osteoarthritis (OA) is a degenerative joint disease involving inflammation, oxidative stress, and extracellular matrix (ECM) degradation, leading to cartilage damage and joint dysfunction. This study aimed to evaluate the chondroprotective effects of intra-articular hydrolyzed collagen in a rat model of knee OA using a dual-compartment biochemical and histological approach. Materials and Methods: Twenty male Sprague-Dawley rats underwent ACL transection to induce osteoarthritis and were randomly assigned to receive intra-articular hydrolyzed collagen or saline once weekly for three weeks. At six weeks, knee joints were evaluated histologically using the Mankin score. Synovial fluid and cartilage homogenates were analyzed via enzyme-linked immunosorbent assay (ELISA) for cytokines, cartilage degradation markers, and oxidative stress indicators. Results: The collagen-treated group demonstrated significantly lower Mankin scores. Levels of pro-inflammatory cytokines, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), as well as cartilage degradation markers, matrix metalloproteinase-13 (MMP-13), C-terminal crosslinked telopeptide of type II collagen (CTX-II), and cartilage oligomeric matrix protein (COMP), were significantly reduced (p < 0.05). Additionally, oxidative stress indicators including inducible nitric oxide synthase (iNOS), total oxidant status (TOS), and oxidative stress index (OSI) were decreased, while total antioxidant status (TAS) was increased in both synovial fluid and cartilage homogenates (p < 0.05). Conclusions: Intra-articular hydrolyzed collagen reduced inflammation, oxidative stress, and extracellular matrix (ECM) degradation, indicating potential chondroprotective effects across both synovial and cartilage compartments. Full article

The Pacific white shrimp, Litopenaeus vannamei (L. vannamei), is an important aquaculture species, yet the molecular mechanisms underlying its sex differentiation and gonadal development remain poorly understood. A deeper understanding of these processes is critical for advancing broodstock quality and enabling unisex breeding strategies. While previous studies have focused on gene expression differences between females and males, structural differences in transcriptomic regulation between sexes have been largely overlooked. Here, we present a comprehensive full-length transcriptome analysis of L. vannamei testis and ovary, identifying 830 and 690 novel genes, respectively, and over 6000 new isoforms. Notably, we discovered extensive alternative splicing (AS) events, with the cartilage oligomeric matrix protein-like gene exhibiting over 300 AS isoforms in the ovary compared to only 2 in the testis, suggesting a potential role in ovarian development. Furthermore, sex-determining genes such as Fem-1a, Fem-1c, and Sxl were found to produce AS isoforms exclusively in ovarian tissue. We also identified three germ cell development-associated genes—MAD2-like, RAD51-like, and Su(dx)-like—that undergo distinct AS events in gonadal tissues, leading to sex-specific structural domain alterations. These findings highlight the complexity of AS-mediated post-transcriptional regulation in L. vannamei and provide novel insights into the molecular mechanisms governing sex differentiation and gonadal development. Full article

Cadmium (Cd) is a toxic, non-essential metal that primarily enters animal bodies through the digestive and respiratory systems, leading to damage to multiple organs and tissues. Cd can accumulate in cartilage and induce damage to chondrocytes. Procyanidins (PAs), also known as concentrated tannic acid or oligomeric proanthocyanidins (OPCs), exhibit diverse biological and pharmacological activities. However, the mechanism of OPCs alleviates Cd-induced damage to chondrocytes in chickens remains to be further explored in vitro. Chondrocytes were isolated from both ends of the tibia of 17-day-old SPF chicken embryos, and then subsequently treated with various concentrations of Cd (0, 1, 2.5, 5, and 10 μmol/L) or OPCs (0, 5, 10, 20, and 40 μmol/L) to investigate the mechanism underlying extracellular matrix (ECM) degradation and damage. Cd reduced cell viability, glycosaminoglycan (GAG) secretion, and ECM degradation in chondrocytes by decreasing the expression of type II collagen alpha 1 (COL2A1) and aggrecan (ACAN) while increasing the release of cartilage oligomeric matrix protein (COMP), along with elevated levels of matrix-degrading enzymes, such as matrix metalloproteinases 1 (MMP1), MMP10, and MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5. Cd induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and the expression of matrix-degrading enzymes, impairing ECM synthesis, an effect that could be alleviated by ERK1/2 inhibitor U0126. Chondrocytes were treated with 5 μmol/L Cd and 10 μmol/L OPCs, and it was found that OPCs inhibited the activation of the ERK1/2 signaling pathway and the expression of matrix-degrading enzymes, while promoting ECM synthesis and alleviating Cd-induced ECM damage in chickens. This study provides a theoretical basis for clinical research on OPCs with respect to the prevention and treatment of Cd-induced chondrogenic diseases in poultry. Full article