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Cartilage[JOURNAL]

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Identification of Serum Biomarkers for Early-Stage Knee Osteoarthritis Using Proteomics in a Murine Model of Osteoarthritis.

Yamauchi S, Sasaki E, Tatara Y … +5 more , Ishibashi K, Tsushima T, Kimura Y, Tsuda E, Ishibashi Y

Cartilage · 2025 Aug · PMID 40781794 · Full text

ObjectiveTo characterize the serum protein profiles of osteoarthritis model mice, particularly mice with early-stage osteoarthritis, using liquid chromatography-mass spectrometry (LC-MS/MS).DesignSerum and knee samples w... ObjectiveTo characterize the serum protein profiles of osteoarthritis model mice, particularly mice with early-stage osteoarthritis, using liquid chromatography-mass spectrometry (LC-MS/MS).DesignSerum and knee samples were collected from 5 control mice and 15 osteoarthritis model mice that underwent destabilization of the medial meniscus (DMM). Osteoarthritic knee samples were collected 4, 8, and 12 weeks after DMM. Knee osteoarthritis severity was scored using the Osteoarthritis Research Society International (OARSI) scoring system. All serum samples were analyzed via LC-MS/MS after removing highly abundant proteins using a ProteoMiner kit (Bio-Rad).ResultsThe average OARSI scores of the medial tibial plateau and medial femoral condyle at 8 weeks after DMM (3.40 ± 1.02 points, = 0.03; 2.60 ± 1.71 points, = 0.03) and 12 weeks after DMM (8.30 ± 3.12 points, = 0.03; 4.80 ± 0.75 points, = 0.03) were significantly higher than the corresponding values in the control group. Compared to those in the control model, 15, 35, and 56 proteins showed different expression levels at 4, 8, and 12 weeks after DMM, respectively. Differentially expressed proteins at 4 weeks after DMM included adenylate kinase, type IV intermediate filament protein, nestin, and insulin-like growth factor-binding proteins. The pathways activated at 4 weeks after DMM differed from those activated at 8 and 12 weeks after DMM.ConclusionProtein expression and activation pathways in the osteoarthritis model differed from those in the control model. Several proteins differentially expressed at 4 weeks postoperatively may be involved in the pathogenesis of osteoarthritis and serve as potential biomarkers of early-stage osteoarthritis.

Five-Year Clinical and MRI-Based Outcomes After Cartilage Repair With or Without ACL Reconstruction: Worse Clinical Outcome after ACL Reconstruction Does not Affect Cartilage Repair Tissue Quality.

Koenig FRM, Vetchy V, Wollner G … +7 more , Kern M, Raudner M, Janacova V, Juras V, Szomolanyi P, Schreiner MM, Trattnig S

Cartilage · 2025 Aug · PMID 40778441 · Full text

ObjectivesCartilage repair (CR) surgery and anterior cruciate ligament reconstruction (ACL-R) are common joint procedures, particularly in younger patients. However, the impact of prior or concurrent ACL-R on the outcome... ObjectivesCartilage repair (CR) surgery and anterior cruciate ligament reconstruction (ACL-R) are common joint procedures, particularly in younger patients. However, the impact of prior or concurrent ACL-R on the outcomes of CR remains uncertain. This study aimed to evaluate whether ACL-R affects the structural quality and clinical outcomes of CR tissue.MethodsIn this retrospective multicenter study, 71 patients undergoing CR were followed up with magnetic resonance imaging (MRI) and clinical evaluations at 3, 12, and 60 months. Of these, 22 patients underwent ACL-R before or during CR. Morphological assessment was performed using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 scores; compositional analysis included T2 mapping ( = 45). Patient-reported outcome measures (PROM) were assessed at all time points. Statistical tests included the Mann-Whitney -test, Wilcoxon signed-rank test, and simulation-based power analysis.ResultsMOCART 2.0 scores and T2 mapping values showed no significant group differences at any time point. Both groups demonstrated significant improvements in PROMs from baseline to 60 months. However, at 60 months, the ACL-R group had significantly lower PROMs than the non-ACL-R group.ConclusionAlthough long-term clinical outcomes were worse in patients with ACL-R, all PROMs improved significantly from baseline to 60 months in both groups. MRI showed no significant differences in focal CR tissue quality, suggesting structural success regardless of ACL-R. While ACL-R patients remain at higher risk of joint degeneration, they can still experience mid-term clinical benefit from CR. These findings support its use in ACL-R patients when joint function is properly restored and expectations are managed.

Magnetic Resonance Imaging Derived Cartilage Morphological Changes and their Correlation with Patient-Reported Outcome Measures Following Knee Joint Distraction for Osteoarthritis: A 12-Month Cohort Study.

Lineham B, Joumah A, Hamilton T … +2 more , Wijayathunga N, Pandit H

Cartilage · 2025 Aug · PMID 40757956 · Full text

AimsKnee osteoarthritis (OA) is a significant source of morbidity and socioeconomic burden, exacerbated by aging populations and rising body mass index. Total Knee Replacement (TKR) is effective but may result in dissati... AimsKnee osteoarthritis (OA) is a significant source of morbidity and socioeconomic burden, exacerbated by aging populations and rising body mass index. Total Knee Replacement (TKR) is effective but may result in dissatisfaction or revision, particularly in young patients. Knee Joint Distraction (KJD) offers a joint-preserving alternative that may delay or avoid replacement. This study assessed cartilage morphology changes using magnetic resonance imaging (MRI) of patients up to 1-year post-KJD in patients from a randomized controlled trial (RCT). The primary aim was to evaluate cartilage volumes at 12 months post-KJD. Secondary aims were to evaluate additional MRI parameters for cartilage morphology and compare the MRI parameters with Patient-Reported Outcome Measure (PROM) scores at 3 and 12 months.MethodsA subset of participants from an RCT comparing TKR and KJD were analyzed. The MRI and PROMs, including Knee Injury & Osteoarthritis Outcomes Score (KOOS), Oxford Knee Score (OKS), and pain visual analogue scale (VAS), were collected at baseline, 3 months, and 12 months postintervention. Cartilage segmentation using commercial software and grading using the MRI Osteoarthritis Knee Score (MOAKS) were performed.ResultsTen patients were included. Increases in mean cartilage volume were observed in all regions except the trochlear at both follow-ups. Mean cartilage thickness increased in all areas except the lateral tibia. Mean denuded bone area decreased in all regions at 12 months and in the lateral femur at 3 months. Baseline cartilage status was predictive of treatment response.ConclusionKJD led to improvements in cartilage morphology up to 12 months, suggesting its potential as a joint-preserving strategy for knee OA. Further long-term studies are needed to confirm benefits and understand mechanisms.

miR-708-5p Attenuates Osteoarthritis Progression via Multi-Target Modulation of the NOX4/NF-κB Axis and Cartilage Homeostasis.

Huang SH, Liu ZM, Chen SJ … +6 more , Tu PY, Tien YC, Lu CC, Wang CC, Chen LM, Shen PC

Cartilage · 2025 Jul · PMID 40734512 · Full text

ObjectiveTo investigate the novel role of miR-708-5p in osteoarthritis (OA) and its potential as a therapeutic target through regulation of NOX4/NF-κB signaling.MethodsExpression levels of miR-708-5p were analyzed in OA... ObjectiveTo investigate the novel role of miR-708-5p in osteoarthritis (OA) and its potential as a therapeutic target through regulation of NOX4/NF-κB signaling.MethodsExpression levels of miR-708-5p were analyzed in OA cartilage using GEO datasets and validated in interleukin (IL)-1β-treated primary human chondrocytes. Gain- and loss-of-function experiments were performed using miR-708-5p mimics and inhibitors to evaluate its effects on inflammation, extracellular matrix metabolism, apoptosis, and oxidative stress. Direct targeting of NOX4 by miR-708-5p was confirmed through bioinformatic prediction, luciferase reporter assays, and rescue experiments.ResultsmiR-708-5p was significantly downregulated in OA cartilage and IL-1β-treated chondrocytes. Overexpression of miR-708-5p attenuated IL-1β-induced inflammatory responses by suppressing pro-inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor [TNF]-α), inhibiting matrix-degrading enzymes (MMP3, ADAMTS-4), and enhancing anabolic factors (COL2A1, SOX9). miR-708-5p protected against chondrocyte apoptosis by regulating Bcl2/BAX and caspase-3 expression. It also increased chondrocyte proliferation in EdU assays and reduced reactive oxygen species (ROS) production. Mechanistically, miR-708-5p directly inhibited NOX4, reducing ROS generation and nuclear factor kappa B (NF-κB) activation. NOX4 overexpression reversed the protective effects of miR-708-5p, confirming the functional significance of this regulatory axis.ConclusionmiR-708-5p is downregulated in OA and exerts chondroprotective effects. These findings suggest that restoring miR-708-5p expression may effectively suppress the NOX4/NF-κB axis and modulate chondrocyte inflammation, oxidative stress, apoptosis, and matrix degradation.

Comparison of Magnetic Resonance Observation of Cartilage Repair Tissue Score and Functional Outcomes between Microdrilling and Microfracture for Cartilage Lesions of Distal Femur: A Retrospective Comparative Study.

Byun J, Jung M, Chung K … +4 more , Moon HS, Jung SH, Kim JK, Kim SH

Cartilage · 2025 Jul · PMID 40726403 · Full text

ObjectiveThis study aimed to compare the clinical outcomes of microdrilling and microfracture for unipolar cartilage lesions of the distal femur.DesignPatients who underwent either microfracture or microdrilling and had... ObjectiveThis study aimed to compare the clinical outcomes of microdrilling and microfracture for unipolar cartilage lesions of the distal femur.DesignPatients who underwent either microfracture or microdrilling and had postoperative magnetic resonance imaging (MRI) at 1 year were retrospectively reviewed. The morphology of the repaired cartilage tissue was evaluated using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score. Functional outcomes were assessed using the International Knee Documentation Committee (IKDC) subjective, Lysholm scores, and Visual Analog Scale (VAS). In addition, the proportion of patients achieving improvement beyond the minimal clinically important difference (MCID) was analyzed.ResultsThe MOCART score was significantly higher in the microdrilling group. Among the variables, volume fill of the cartilage defect and integration into the adjacent cartilage showed significantly better results in favor of the microdrilling group. A higher proportion of patients achieved improvement in the IKDC subjective score beyond the MCID in the microdrilling group, whereas no significant differences were observed between the groups in Lyholm score and VAS.ConclusionMicrodrilling showed better outcomes in terms of the MOCART and IDKC subjective scores than microfracture, whereas Lysholm and VAS showed no significant differences. Further prospective studies are required to evaluate the results of these 2 procedures.

Intra-articular Injections of Allogeneic Platelet-Rich Plasma from Responder Patients for the Treatment of Knee Osteoarthritis: A Pilot and Feasibility Clinical Trial.

Sánchez M, Guadilla J, Jorquera C … +11 more , Marijuán-Pinel D, Mercader-Ruiz J, Beitia M, Andrade R, Espregueira-Mendes J, González S, Oraa J, López de Dicastillo L, Fiz N, Azofra J, Delgado D

Cartilage · 2025 Jul · PMID 40726366 · Full text

ObjectiveTo evaluate the feasibility, safety and efficacy of allogeneic platelet-rich plasma (PRP) from responder donors to treat knee osteoarthritis (KOA) patients who showed negative response to autologous PRP.DesignTh... ObjectiveTo evaluate the feasibility, safety and efficacy of allogeneic platelet-rich plasma (PRP) from responder donors to treat knee osteoarthritis (KOA) patients who showed negative response to autologous PRP.DesignThis pilot feasibility trial included KOA patients who did not respond to previous autologous PRP treatment. They were treated with intra-articular injections of allogeneic PRP from responder donors. Patients filled out Knee injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), and Lequesne Index at baseline, 2, 6, and 12 months. Blood and PRP from donors and patients were analyzed, and a cell proliferation study was carried out.ResultsOf the 16 patients enrolled, 14 completed the study. KOOS pain subscale and VAS showed a significant increase from baseline to 12 months, and the Lequesne Index to 6 months ( < .005). Six patients (42.9%) showed a Minimal Clinically Important Improvement. No adverse reactions to allogeneic PRP were reported. The platelet number between donors and recipients was similar ( > .05) with a platelet concentration factor of 2.5. Donors were significantly younger than patients ( < .05) and presented higher levels of IGF-1 ( < .05). Cell bioactivity showed no differences between patient and donor PRP ( > .05).ConclusionThe use of allogeneic PRP from donor responders is a feasible and safe treatment for KOA patients who do not respond to autologous PRP. This treatment showed efficacy after 1 year of follow-up, suggesting a valid alternative for these patients, although further research is needed.EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/). Registration number: 2021-001267-24.

Cartilage Injuries of the Ankle: New Beginnings.

Kerkhoffs GMMJ, Kennedy JG, Brittberg M … +1 more , Dahmen J

Cartilage · 2026 Mar · PMID 40708317 · Full text

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Outcomes After Initial Non-Operative Treatment of Osteochondral Lesions of the Talus (OLT) in Skeletally Immature Patients: A Cross-Sectional Study.

Steman JAH, Buck TMF, Dahmen J … +3 more , Struijs PAA, Stufkens SAS, Kerkhoffs GMMJ

Cartilage · 2025 Jul · PMID 40698643 · Full text

IntroductionLiterature on treatment outcomes in skeletally immature patients with osteochondral lesions of the talus (OLT) is scarce. As the healing of an OLT may be fundamentally different in a skeletally immature patie... IntroductionLiterature on treatment outcomes in skeletally immature patients with osteochondral lesions of the talus (OLT) is scarce. As the healing of an OLT may be fundamentally different in a skeletally immature patient, more evidence is required focusing on this specific patient group. The primary aim of this study is to assess the conversion to surgery rate after initial non-operative management in skeletally immature patients with an OLT. The secondary aims of the present study are to assess and compare the clinical outcomes and reoperations after both non-operative and surgical treatment strategies at a mid- to long-term follow-up.MethodsAll skeletally immature patients at the moment of initial treatment, treated for their primary or non-primary OLT with a minimum follow-up duration of 2 years, were included in this study. Patients with concomitant injuries were excluded. All patients started with non-operative management. In case of failure of non-operative management, patients converted to Bone Marrow Stimulation (BMS) or fixation. The primary outcome was the conversion to surgery rate after initial non-operative management. Secondary outcomes consist of reoperations at mature and immature age, pain during weight bearing, measured by the numeric rating scale (NRS), NRS of pain during rest, NRS during stair climbing, Berndt and Harty outcome question, Foot and Ankle Outcome Score (FAOS) and Short Form-36 (SF-36) and the patient satisfaction rate regarding the received treatment.ResultsA total of 52 patients, 54% female, mean age of 13.6 years, were included in this study. Median follow-up duration was 81 months (range = 24-265 months). Seventeen patients received non-operative treatment as final treatment. In total, 35 (67%) out of 52 patients required surgical treatment after initial non-operative management, of which 14 underwent BMS and 20 had fixation while skeletally immature, 1 patient that had surgical treatment as an adult was excluded for further analysis. The median NRS of pain during weight bearing was 1 (interquartile range [IQR] = 0-2), 1 (IQR = 0-3), and 0 (IQR = 0-0.5) in the (sustained) non-operative, BMS, and fixation groups, respectively ( < 0.012). No significant differences in clinical outcomes between the different treatment groups could be observed. No complications occurred after surgical treatment. Reoperation rates were 21% and 20% in the BMS and fixation groups, respectively.ConclusionsThe most important finding of this study is that 67% of the patients receiving initial non-operative management for OLTs ultimately required surgery.Level of evidenceLevel III, cross-sectional comparative study.

Arthroscopic Non-Concentrated Autologous Iliac Bone Marrow Stimulation Shows Stable Medium-Term Clinical and Radiological Outcomes for Small Cystic Talar Osteochondral Lesions.

Zheng B, Yan F, Zhong Y … +3 more , Wei S, Wu H, Xu F

Cartilage · 2025 Jul · PMID 40674179 · Full text

ObjectiveTo evaluate radiological, short-term, and medium-term clinical outcomes of arthroscopic non-concentrated iliac bone marrow stimulation (BMS) for small talar cystic osteochondral lesions of the talus (OLTs).Desig... ObjectiveTo evaluate radiological, short-term, and medium-term clinical outcomes of arthroscopic non-concentrated iliac bone marrow stimulation (BMS) for small talar cystic osteochondral lesions of the talus (OLTs).DesignForty-three cases underwent this modified BMS between 2014 and 2019 were evaluated. Clinical outcomes were assessed by the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) and Sports Subscales (SS). Regenerated tissue was evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue scales (MOCART-2.0). Subgroup analysis based on locations and concomitant anterior talofibular ligament (ATFL) injuries.ResultsThe average diameter and depth of cysts were 6.97 ± 1.53 mm and 5.47 ± 1.10 mm, respectively. At a mean follow-up of 57.02 ± 19.61 months, FAAM-ADL and FAAM-SS improved significantly (45.65 ± 4.56 to 74.77 ± 8.03 and 12.63 ± 1.87 to 26.67 ± 3.41, respectively). From short-term to medium-term, FAAM-ADL revealed a minor decline (75.53 ± 7.76 vs. 74.77 ± 8.03, = 0.421); FAAM-SS improved (25.37 ± 3.51 vs. 26.67 ± 3.41, = 0.089). Medial lesions demonstrated favorable outcomes compared to lateral lesions [FAAM-ADL (77.04 ± 7.23 vs. 70.75 ± 8.10, = 0.013), FAAM-SS (28.08 ± 2.40 vs. 24.19 ± 3.51, < 0.001), and MOCART-2.0 (85.19 ± 11.27 vs. 71.88 ± 11.09, < 0.001)]. Lateral lesions indicated higher rates of major hypertrophy (56.25% vs. 7.69%) and split-like defects (56.25% vs. 15.38%). The ATFL injuries did not significantly influence revision rates (15.8% vs. 4.2%, = 0.439).ConclusionsArthroscopic non-concentrated iliac BMS demonstrated stable outcomes for small cystic OLTs. Lateral lesions were associated with inferior subjective scores and relatively higher rates of irregular fibrocartilage.

Impact of Vascular Endothelial Growth Factor Concentration on the Short-term Efficacy of Platelet-Rich Plasma (PRP) Therapy for Knee Osteoarthritis.

Yamamoto N, Saita Y, Kobayashi Y … +7 more , Wakayama T, Uchino S, Momoi Y, Nakajima R, Ohtaki T, Kaneko H, Ishijima M

Cartilage · 2025 Jul · PMID 40616420 · Full text

IntroductionThis study investigates the association between vascular endothelial growth factor (VEGF) levels and platelet-rich plasma (PRP) treatment outcomes, as well as the role of other cytokines in symptom improvemen... IntroductionThis study investigates the association between vascular endothelial growth factor (VEGF) levels and platelet-rich plasma (PRP) treatment outcomes, as well as the role of other cytokines in symptom improvement.MethodsThirty-nine patients with knee osteoarthritis (KOA) who underwent PRP therapy were analyzed. Cytokine and growth factor levels in PRP were measured, and clinical outcomes were assessed using the visual analog scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) before and 1 month after a single intra-articular PRP injection. Correlations between cytokine levels and clinical improvements were evaluated.ResultsAge correlated positively with C-X-C motif chemokine ligand 9 (CXCL9) (r = 0.50, p < 0.001). Body mass index (BMI) correlated negatively with interleukin-10 (IL-10) and positively with interleukin-18 (IL-18). Elevated IL-18 levels correlated with worse KOOS-Activities of Daily Living (ADL) improvements (r = -0.410, = 0.01), linking obesity, inflammation, and reduced PRP efficacy. While VEGF showed no association with patient background, higher VEGF levels correlated with poorer VAS score improvements (r = -0.381, = 0.017), suggesting reduced PRP efficacy. A VEGF cut-off of 120 pg/ml identified non-responders with 82.6% sensitivity, 56.2% specificity, and an area under the curve (AUC) of 0.71. Among patients with VEGF ≥120 pg/ml, the response rate was 26.9%, while those with VEGF <120 pg/ml had 75%.ConclusionsHigher VEGF concentrations in PRP were associated with reduced short-term clinical efficacy in patients with knee osteoarthritis. VEGF may serve as a predictive biomarker for PRP treatment response.

Medial Meniscus Posterior Horn Horizontal Tears are Associated with Knee Posteromedial Impinging Structures Inducing Shearing Forces in Patients with Meniscus Degeneration.

Lim S, Chung JY, Park JY … +3 more , Yun HW, Noh S, Park DY

Cartilage · 2025 Jul · PMID 40605817 · Full text

PurposeThis study aimed to identify potential impinging and shear stress-inducing factors in knees with medial meniscus posterior horn horizontal tears (MMPHHT) using magnetic resonance imaging (MRI) in middle-aged patie... PurposeThis study aimed to identify potential impinging and shear stress-inducing factors in knees with medial meniscus posterior horn horizontal tears (MMPHHT) using magnetic resonance imaging (MRI) in middle-aged patients with meniscal degeneration.Materials and MethodsWe retrospectively analyzed and compared consecutive patients with MMPH signal changes or MMPHHT on MRI from January 2015 to January 2022. After 1:1 propensity score matching, 80 patients in each group were analyzed. Bony impinging factors, including the femoral condylar offset ratio, the ratio of posterior condylar offset (PCO) to tibial width, posterior medial tibial plateau concavity, and the medial tibial slope, were assessed. Soft tissue impinging factors, such as the MMPH coverage ratio, presence of medial femoral condyle focal cartilage defects or posterior tibial osteophytes, were also analyzed.ResultsDemographic data did not differ between MMPHHT and MMPH signal change groups. MMPHHT group showed increased medial tibial slope (5.33 ± 2.05° vs 4.21 ± 2.58°, = .003), higher incidence of posterior medial tibial plateau concavity ( = .040), greater MMPH coverage ratio (0.43% ± 0.05% vs 0.41% ± 0.04%, = .022), and more posterior tibial osteophytes ( = .012). Multivariate logistic regression identified higher medial tibial slope (OR = 1.288, = .016), MMPH coverage ratio (OR = 1.369 × 10, = .020), and posterior tibial osteophytes (OR = 4.525, = .009) as independent factors associated with MMPHHT.ConclusionIn conclusion, we have determined several anatomical contributing factors related to MMPHHT. Such factors may be useful in understanding the progression of meniscus degeneration in early OA knees. Furthermore, addressing correctable factors during surgery such as tibia slope correction or osteophytectomy may improve repair results of MMPHHT in the future.

Differentiation of Human Induced Pluripotent Stem Cells Toward Implantable Chondroprogenitor Cells.

Ekholm J, Vukusic K, Brantsing C … +7 more , Shaw G, Ur Rehman Bhatti F, Simonsson S, Falk A, Murphy M, Rotter Sopasakis V, Lindahl A

Cartilage · 2025 Jul · PMID 40605688 · Full text

Post-traumatic chondral and osteochondral lesions can be treated with autologous chondrocyte implantation (ACI), but the high cost of autologous cell expansion under strict Good Manufacturing Practice (GMP) regulations l... Post-traumatic chondral and osteochondral lesions can be treated with autologous chondrocyte implantation (ACI), but the high cost of autologous cell expansion under strict Good Manufacturing Practice (GMP) regulations limits patient access. Stem cell-based advanced therapy medicinal products (ATMPs) offer more cost-effective alternatives, with human induced pluripotent stem cells (iPSC) showing great promise due to their expandability, low immunogenicity, commercialization potential, and fewer ethical concerns. To develop a protocol to direct iPSC through a mesenchymal stage into chondroprogenitors (iCHOp), resembling autologous chondroprogenitor cells used in ACI. The derived chondroprogenitor cells were expanded in monolayer and in 3-dimensional (3D) cultures and subsequently analyzed using transcriptomic profiling via RNA sequencing and reverse transcription quantitative polymerase chain reaction and compared with ACI chondrocytes. Transcriptomic profiling confirmed successful differentiation, with iCHOp showing 83% similarity to ACI chondrocytes. Further 3D culture maturation led to upregulation of chondrogenesis-related genes and activation of cartilage-specific pathways. Histological analysis confirmed extracellular matrix production, including proteoglycans, collagen, and versican. Furthermore, the protocol's reproducibility was demonstrated using 3 distinct iPSC lines, successfully expanded in both serum-containing and defined serum-free media. Our optimized approach yields iCHOp with phenotypes closely matching ACI chondrocytes, offering a solid foundation for further development and potential clinical applications in cartilage repair.

Direct Fixation of Acute Chondral-Only Fragments in Young Patients.

Walker PB, Araujo G, Sridharan M … +5 more , Edogun E, Sheppard WL, Kremen TJ, Fabricant PD, Jones KJ

Cartilage · 2025 Jul · PMID 40590335 · Full text

IntroductionCartilage lesions of the knee frequently result from acute traumatic injuries and pose significant challenges, particularly in young and active patients. While many involve osteochondral lesions, isolated cho... IntroductionCartilage lesions of the knee frequently result from acute traumatic injuries and pose significant challenges, particularly in young and active patients. While many involve osteochondral lesions, isolated chondral defects also occur. Traditional treatment focuses on fixation when viable subchondral bone is present; however, managing chondral-only lesions remains controversial due to limited intrinsic healing capacity.MethodsA systematic review was conducted, screening over 300 studies since August 2023. Inclusion criteria required (1) English-language studies, (2) reports on isolated chondral fragment fixation, and (3) a minimum of 6 months of follow-up. Eighteen studies met these criteria. Data on patient demographics, lesion characteristics, fixation methods, clinical outcomes, and functional scores were extracted.ResultsA total of 76 patients (mean age: 14.3 ± 3.7 years) were analyzed. Males comprised 80.3% of the cohort. The mean follow-up was 40.3 months (range: 7-171), and the mean chondral fragment size was 4.28 cm. The most common lesion locations were the lateral femoral condyle (34.2%), trochlea (32.2%), patella (25%), and medial femoral condyle (8.6%). Healing occurred in 96% of cases, and 86% of patients returned to sports at an average of 10.3 ± 6.1 months. Younger patients (≤14 years) had a significantly higher RTS rate (OR: 5.8; = 0.0427). Functional scores (IKDC, KOOS, Marx, Tegner) demonstrated excellent postoperative outcomes.ConclusionDespite prior concerns regarding chondral-only fixation, this study demonstrates high healing rates and favorable functional outcomes. Direct fixation is a viable strategy, particularly in adolescents and young adults. Further prospective trials are needed to validate these findings.

The Use of Collagen-Based Filler for Trapeziometacarpal Osteoarthritis: Long-Term Follow-Up and Future Applications.

Corain M, Faccioli N, Lavagnolo U

Cartilage · 2025 Jul · PMID 40590316 · Full text

BackgroundTrapeziometacarpal osteoarthritis (TMO) is a prevalent degenerative condition. While conservative treatments such as physiotherapy, drugs, and corticosteroid or hyaluronic acid injections offer symptomatic reli... BackgroundTrapeziometacarpal osteoarthritis (TMO) is a prevalent degenerative condition. While conservative treatments such as physiotherapy, drugs, and corticosteroid or hyaluronic acid injections offer symptomatic relief, their long-term efficacy remains debated. A recent study has explored collagen-based fillers as an alternative, but long-term clinical outcomes are still under investigation.MethodsThis study enrolled 64 patients diagnosed with TMO, stratified into 2 groups based on the Eaton-Littler classification (grade 1-2: group A; grade 3-4: group B). All patients received a percutaneous intra-articular injection of a cell-free collagenic hydrogel under ultrasound guidance. Outcomes were assessed more than 2 years using the Numeric Rating Scale (NRS) for pain, Jamar and Pinch tests for grip strength, and the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire.ResultsIn both groups, all studied variables demonstrated a significant improvement ( < 0.001) that was sustained in the long term. Notably, greater improvement was observed in strength tests for Group A patients and in the DASH score for Group B patients. The most substantial improvement occurred between 2 and 6 months post-procedure. No adverse events were reported.ConclusionCollagen-based filler injections provide long-term pain relief and functional improvement in TMO, representing a promising minimally invasive treatment option.Trial registry name:NCT06881186.

Inhibition of Toll-Like Receptor 3 Relieves Osteoarthritis by Suppression of Cartilage Degradation, Nuclear Factor Kappa B-Mediated Inflammation, and Activation of Autophagy.

Hou Z, Wang M, Cao S

Cartilage · 2025 Jun · PMID 40553578 · Full text

OBJECTIVE: To investigate the regulatory role of Toll-like receptor 3 (TLR3) in osteoarthritis (OA) progression, particularly its impacts on cartilage degradation, NF-κB-mediated inflammation, and autophagy activation. M... OBJECTIVE: To investigate the regulatory role of Toll-like receptor 3 (TLR3) in osteoarthritis (OA) progression, particularly its impacts on cartilage degradation, NF-κB-mediated inflammation, and autophagy activation. METHOD: 1. Model Constuction: OA mouse model generated via anterior cruciate ligament transection (ACLT); LPS-induced inflammatory injury in murine ATDC5 chondrocytes; Histomorphological analysis of cartilage tissue using H&E and Safranine O staining. 2. Molecular Detection: TLR3 expression assessed by Western blot; Cartilage degradation markers (MMP-13, ADAMTS) and NF-κB pathway proteins analyzed via Western blot; Pro-inflammatory cytokine levels (IL-1β, TNF-α) quantified via RT-qPCR and Western blot. 3. Functional Assays: Cell viability examined via CCK-8 assay. RESULTS: 1. TLR3 Upregulation: TLR3 was highly expressed in OA cartilage and LPS-treated chondrocytes. 2. Cartilage Protection: TLR3 inhibition reduced cartilage erosion and proteoglycan loss in ACLT mice (confirmed by H&E and Safranine O staining); Downregulation of cartilage degradation markers (MMP-13, ADAMTS-5) observed in TLR3-knockdown models. 3. Anti-inflammatory Effects: TLR3 knockdown suppressed NF-κB activation, reducing IL-1β and TNF-α levels. 4. Autophagy Activation: Enhanced LC3-II/LC3-I ratio and Beclin-1 expression indicated TLR3 inhibition promotes autophagy. CONCLUSION: TLR3 drives OA progression through dual mechanisms: 1. Pro-inflammatory Pathway: Activates NF-κB signaling to amplify cytokine release and cartilage matrix breakdown. 2. Autophagy Suppression: Inhibits autophagy-related proteins, impairing cellular homeostasis. Targeting TLR3 may represent a therapeutic strategy to balance inflammation and autophagy, potentially slowing OA progression in multi-joint involvement cases.

KDM3A Modulates Biological Processes in Osteoarthritis Cell Models Via the Wnt/β-Catenin Signaling Pathway.

Fu Y, Yi S, Peng Q … +2 more , Jiang H, Zhou J

Cartilage · 2025 Jun · PMID 40542702 · Full text

BackgroundOsteoarthritis (OA) is a chronic disease that seriously affects human health. Although biomarkers are vital to the discovery and therapy of OA, current research on OA-specific biomarkers remains limited, indica... BackgroundOsteoarthritis (OA) is a chronic disease that seriously affects human health. Although biomarkers are vital to the discovery and therapy of OA, current research on OA-specific biomarkers remains limited, indicating a need for further expansion of this field of study.MethodsIn this study, differential genes in OA patients and normal samples in Genomics Expression Omnibus (GEO) database were analyzed for signaling pathway enrichment. Then, Weighted Gene Co-expression Network Analysis (WGCNA) combined with Least Absolute Shrinkage and Selection Operator (LASSO) analysis was used to obtain key genes associated with OA diagnosis, including BCL6 co-repressor (BCOR), Coiled-Coil Domain Containing 59 (CCDC59), Jun Proto-Oncogene (JUN), Lysine Demethylase 3A (KDM3A), L3MBTL Histone Methyl-Lysine Binding Protein 4 (L3MBTL4) and Zinc Finger Protein 292 (ZNF292). Finally, the role of KDM3A in OA cell model was verified by constructing KDM3A overexpression and silencing cell lines.ResultsIt was found that overexpression of KDM3A significantly downregulated β-catenin expression compared with the oe-NC group, thus affecting a series of biological processes in the OA cell model, specifically, increasing antioxidant capacity, reducing levels of inflammatory factors, and inhibiting extracellular matrix degradation.ConclusionThis study not only provided six key target genes for OA but also revealed the important role of KDM3A in OA, providing a reference for gene targeted therapy for OA patients.

Cellular Senescence in Human Chondrocytes in Relation to Osteoarthritis.

Qiang Y, Zheng C, Maslov AY … +6 more , Lu Z, Zhou M, Gao J, Ren P, Pang Y, Vijg J

Cartilage · 2025 Jun · PMID 40521922 · Full text

IntroductionCellular senescence, i.e., a state of permanent cessation of cell division, is a hallmark of aging and has been associated with age-related diseases, most notably osteoarthritis (OA). Here we assessed senesce... IntroductionCellular senescence, i.e., a state of permanent cessation of cell division, is a hallmark of aging and has been associated with age-related diseases, most notably osteoarthritis (OA). Here we assessed senescence in chondrocytes, first after treatment with the mutagens N-ethyl-N-nitrosourea (ENU) or bleomycin, and then in in cartilage samples from OA patients and control subjects.MethodsCellular senescence in cultured chondrocytes treated with mutagens was assessed by senescence-associated β-galactosidase (SA-β-gal) staining and by evaluating the expression levels of and . Cellular senescence in human hip cartilage chondrocytes from OA patients or non-OA controls was similarly evaluated. Apoptosis was measured by the / expression ratio, and by both TUNEL assay and the / ratio.ResultsIn human articular cartilage, senescent cells were found to be significantly elevated in OA lesions of patients as compared with normal cartilage of non-OA control subjects. , senescence was observed in bleomycin-treated chondrocytes, but not in ENU-treated cells.ConclusionsOur findings demonstrate that cellular senescence is associated with the pathogenesis of OA, with DNA damage and mutations as potential contributing factors in OA-associated senescence.

BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization Through PINK1/Parkin Signaling Pathway: Focus on Immune Responses in the Perichondrium.

Klabukov I, Kisel A, Eygel D … +3 more , Isaeva E, Yatsenko E, Baranovskii D

Cartilage · 2025 Jun · PMID 40495490 · Full text

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Mir-450a-5p Ameliorates IL-1β-Induced Chondrocyte Apoptosis, Inflammation, and Extracellular Matrix Degradation by Down-Regulating LITAF.

Jia GF, Tan W, Han X

Cartilage · 2025 Jun · PMID 40485220 · Full text

ObjectiveOsteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, causing severe pain and disability. Recent studies suggest that miR-450a-5p may regulate inflammatory pathways in OA. T... ObjectiveOsteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, causing severe pain and disability. Recent studies suggest that miR-450a-5p may regulate inflammatory pathways in OA. This study aimed to elucidate the role of miR-450a-5p in OA, providing a potential therapeutic target for the clinical treatment.MethodsCartilage tissues were collected from OA patients undergoing knee replacement surgery, and CHON-001 cells were treated with interleukin (IL)-1β to induce an OA model . Real-time quantitative polymerase chain reaction was used to detect the miR-450a-5p expression, and Western blot determined the lipopolysaccharide-induced tumor necrosis factor (TNF)-α factor (LITAF) expression. The targeting relationship between LITAF and miR-450a-5p was verified by dual-luciferase reporter assay. Cell proliferation and apoptosis were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. Levels of IL-6, IL-10, and TNF-α were measured via enzyme-linked immunosorbent assay. In addition, Western blot was employed to detect the expressions of matrix metalloproteinase-3 (MMP-3), collagen III, and aggrecan in extracellular matrix (ECM).ResultsMiR-450a-5p expression was significantly down-regulated in OA tissues and IL-1β-induced CHON-001 cells (~60%), while LITAF expression was markedly increased (~1.8-fold). There was a negative correlation between miR-450a-5p and LITAF in OA tissues (r = -0.596, < 0.01). MiR-450a-5p directly targeted and inhibited LITAF expression. Its overexpression promoted chondrocyte proliferation, reduced apoptosis and inflammatory cytokines, and mitigated ECM degradation.ConclusionsMiR-450a-5p inhibited LITAF expression, thereby attenuating apoptosis, inflammation, and ECM degradation in chondrocytes. It may serve as a promising therapeutic target for OA.

ZC3H13 Promotes NSUN4-Mediated Chondrocyte Mitochondrial Dysfunction and Pyroptosis in Temporomandibular Joint Osteoarthritis.

Chen Y, Ren H

Cartilage · 2025 May · PMID 40433805 · Full text

ObjectiveTemporomandibular joint osteoarthritis (TMJOA) seriously influences the quality of life of patients. Chondrocyte mitochondrial dysfunction and pyroptosis play an important role in the development of osteoarthrit... ObjectiveTemporomandibular joint osteoarthritis (TMJOA) seriously influences the quality of life of patients. Chondrocyte mitochondrial dysfunction and pyroptosis play an important role in the development of osteoarthritis, but their role in TMJOA pathogenesis is elusive. We aimed to probe into the role and mechanism of mitochondrial dysfunction and pyroptosis in TMJOA.DesignTMJOA rat models were established by unilateral anterior crossbite operation. Pathological changes in cartilage tissues were observed by hematoxylin-eosin staining, and mitochondrial dysfunction and pyroptosis were evaluated by immunohistochemistry. The biological function and mechanism of ZC3H13 in mitochondrial dysfunction and pyroptosis were determined by cell experiments.ResultsWe discovered that mitochondrial dysfunction and pyroptosis occurred in cartilage tissues of TMJOA rats. The expression of ZC3H13 was observably upregulated in TMJOA rats. Further cell experiments showed that interference of ZC3H13 restrained mitochondrial dysfunction and pyroptosis of chondrocytes. RNA sequencing revealed that NSUN4 expression was significantly increased in chondrocytes after ZC3H13 knockdown. Silencing of ZC3H13 remarkably diminished the level of NSUN4 N6-methyladenosine (m6A) modification. Moreover, mitochondrial dysfunction and pyroptosis of chondrocytes were notably increased after NSUN4 knockdown.ConclusionOur study revealed that ZC3H13-mediated NSUN4 repressed TMJOA progression by modulating chondrocyte mitochondrial dysfunction and pyroptosis in an m6A-dependent manner, which may offer a potential strategy for TMJOA treatment.
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