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The Actin Cytoskeleton as a Regulator of Proteoglycan 4. 肌动蛋白细胞骨架是蛋白聚糖的调节器 4.
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-09-01 Epub Date: 2024-01-06 DOI: 10.1177/19476035231223455
Sofia Gonzalez-Nolde, Cameron J Schweiger, Elizabeth E R Davis, Thomas J Manzoni, Samer M I Hussein, Tannin A Schmidt, Stephanie G Cone, Gregory D Jay, Justin Parreno
{"title":"The Actin Cytoskeleton as a Regulator of Proteoglycan 4.","authors":"Sofia Gonzalez-Nolde, Cameron J Schweiger, Elizabeth E R Davis, Thomas J Manzoni, Samer M I Hussein, Tannin A Schmidt, Stephanie G Cone, Gregory D Jay, Justin Parreno","doi":"10.1177/19476035231223455","DOIUrl":"10.1177/19476035231223455","url":null,"abstract":"<p><p>ObjectiveThe superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton <i>in vitro</i>. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies.Materials and methodsA comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed.ResultsPRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs <i>in vitro</i>. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling.ConclusionActin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an <i>in vivo</i> context to further potential of leveraging actin arrangement to arthritic therapeutics.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"376-387"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139105878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage Loss. 骨髓病变和炎性磁共振成像标记物在两年内的波动以及与软骨定量损失的并发关系
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-09-01 Epub Date: 2024-10-26 DOI: 10.1177/19476035241287694
Frank W Roemer, Mylène P Jansen, Susanne Maschek, Simon C Mastbergen, Anne-Karien Marijnissen, Anna Wisser, Rafael Heiss, Harrie H Weinans, Francisco J Blanco, Francis Berenbaum, Margreet Kloppenburg, Ida K Haugen, Felix Eckstein, David J Hunter, Ali Guermazi, Wolfgang Wirth
{"title":"Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage Loss.","authors":"Frank W Roemer, Mylène P Jansen, Susanne Maschek, Simon C Mastbergen, Anne-Karien Marijnissen, Anna Wisser, Rafael Heiss, Harrie H Weinans, Francisco J Blanco, Francis Berenbaum, Margreet Kloppenburg, Ida K Haugen, Felix Eckstein, David J Hunter, Ali Guermazi, Wolfgang Wirth","doi":"10.1177/19476035241287694","DOIUrl":"10.1177/19476035241287694","url":null,"abstract":"<p><p>ObjectiveTo assess whether change of semiquantitatively magnetic resonance imaging (MRI)-defined bone marrow lesions (BMLs) and inflammatory markers is associated with change in quantitatively-assessed cartilage loss in the femorotibial joint (FTJ) in knees with radiographic osteoarthritis (OA) over 24 months.DesignParticipants were included from the IMI-APPROACH and the Osteoarthritis Initiative FNIH studies. Semiquantitative MRI assessment was performed for BMLs, Hoffa- and effusion-synovitis. Quantitative cartilage thickness measurements were performed manually. Definitions of change included number of subregions with BMLs, change in sum and change in maximum increase in size. Change in Hoffa-synovitis and effusion-synovitis was categorized in addition. Between-group comparisons regarding cartilage loss in the FTJ, medial and lateral compartments were performed using analysis of variance (ANOVA).ResultsA total of 629 participants were included. Knees without any BMLs at baseline (BL) and follow-up (FU) had significantly less cartilage loss compared to the other subgroups. Change in both directions in the sum score of BMLs was associated with increased rates of cartilage loss. Maximum increase in size of BMLs was associated with increased rates of cartilage loss (FTJ increase by 2 grades -0.183 mm, 95% CI [-0.335, -0.031], by 3 grades -0.306 mm, [-0.511, -0.101]). Worsening of Hoffa-synovitis was associated with increased rates of cartilage loss.ConclusionKnees without BMLs at BL and FU showed lowest rates of cartilage loss. Knees with an increase in BML size showed increased rates of concurrent cartilage loss. Approaches with the aim to inhibit BML development, avoidance of increase in size and avoidance of Hoffa-synovitis worsening may have beneficial effects on cartilage loss.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"308-321"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced Superficial Zone Chondrocyte Expansion and Redifferentiation by Culture on Chondrocyte-Derived Decellularized Matrices. 通过培养软骨细胞衍生的脱细胞基质增强浅表区软骨细胞的增殖和再分化。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-08-31 DOI: 10.1177/19476035251369735
Thomas J Manzoni, Anh Ho, Lilly Smull, Valarie C West, Jeffery D V Waters, Karina Lemus, James Adams, Alvin W Su, Justin Parreno
{"title":"Enhanced Superficial Zone Chondrocyte Expansion and Redifferentiation by Culture on Chondrocyte-Derived Decellularized Matrices.","authors":"Thomas J Manzoni, Anh Ho, Lilly Smull, Valarie C West, Jeffery D V Waters, Karina Lemus, James Adams, Alvin W Su, Justin Parreno","doi":"10.1177/19476035251369735","DOIUrl":"10.1177/19476035251369735","url":null,"abstract":"<p><p>BackgroundCell-based therapies to regenerate native-like cartilage are limited by the inability to re-express zone-specific molecules. While monolayer-expanded (passaged) chondrocytes are a clinically approved cell source, the resulting tissues have reduced Proteoglycan-4 (PRG4) expression. This may be due to poor attachment, slow proliferation, and dedifferentiation of superficial zone chondrocytes (SZC) on polystyrene. Optimizing expansion conditions is therefore critical. Chondrocyte-derived decellularized extracellular matrix (CD-ECM) has been shown to enhance proliferation and reduce dedifferentiation of full-thickness chondrocytes, but its effect on SZC remains unknown. We tested the hypothesis that culturing SZC on CD-ECM would improve attachment, proliferation, and reduced dedifferentiation, enabling formation of PRG4-expressing tissue.MethodsPrimary bovine SZC were seeded on polystyrene or CD-ECM. Attachment, expansion rate, and gene expression were evaluated during passaging. Cells from each condition were assessed for their capacity to form PRG4-expressing bioengineered tissue.ResultsPrimary bovine SZC had increased attachment and reached confluency faster on CD-ECM. SZC on CD-ECM were smaller, with fewer actin stress fibers, and exhibited reduced expression of dedifferentiation markers. Furthermore, SZC expanded on CD-ECM were stimulated to form tissues rich in Collagen II and Aggrecan with higher Proteoglycan-4 expression.ConclusionsThe use of CD-ECM for passaging SZC may aid in achieving an adequate number of SZC for bioengineering purposes.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251369735"},"PeriodicalIF":2.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasma Amino Acids Reflect Cartilage Loss, Osteoarthritis Pain, Functional Disability, and Mental Health in a Longitudinal Study with Total Knee Replacement. 在全膝关节置换术的纵向研究中,血浆氨基酸反映软骨丢失、骨关节炎疼痛、功能残疾和心理健康。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-08-10 DOI: 10.1177/19476035251360189
Anne-Mari Mustonen, Laura Säisänen, Lauri Karttunen, Petro Julkunen, Amir Esrafilian, Jusa Reijonen, Jussi Mäki, Heikki Kröger, Jari Arokoski, Petteri Nieminen
{"title":"Plasma Amino Acids Reflect Cartilage Loss, Osteoarthritis Pain, Functional Disability, and Mental Health in a Longitudinal Study with Total Knee Replacement.","authors":"Anne-Mari Mustonen, Laura Säisänen, Lauri Karttunen, Petro Julkunen, Amir Esrafilian, Jusa Reijonen, Jussi Mäki, Heikki Kröger, Jari Arokoski, Petteri Nieminen","doi":"10.1177/19476035251360189","DOIUrl":"10.1177/19476035251360189","url":null,"abstract":"<p><p>ObjectiveBiofluid amino acids (AAs) are potential biomarkers and therapeutic targets for knee osteoarthritis (KOA), a disease continuum of both mechanical and inflammatory aspects. Our aim was to identify AAs that would associate with cartilage degradation, subjectively and objectively assessed joint pain and function, and psychological well-being.DesignFasting blood was sampled from 8 healthy controls at baseline, and from 8 end-stage KOA patients before total knee arthroplasty and 1 year post-operatively. Plasma AA profiles were determined with high-performance liquid chromatography, and the obtained results were analyzed with univariate and multivariate statistical tests, and with pathway analysis by MetaboAnalyst.ResultsCystine, <i>β</i>-alanine, and hydroxylysine emerged as potential biomarkers distinguishing KOA patients from controls, and several metabolic pathways were disturbed in baseline KOA. Total knee arthroplasty reduced pain and improved joint function, but the effects on plasma AA metabolism were less obvious. There were significant associations between systemic AA levels and articular cartilage thickness, KOA pain, physical performance, corticospinal excitability, and mental health, independent of age and body adiposity.ConclusionThe results suggest that AA metabolism could play a role in KOA pathophysiology and motivate further studies investigating the potential of AAs as diagnostic biomarkers and therapeutic targets.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251360189"},"PeriodicalIF":2.7,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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. 有或没有前交叉韧带重建的软骨修复后5年临床和mri结果:前交叉韧带重建后较差的临床结果不影响软骨修复组织质量。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-08-08 DOI: 10.1177/19476035251362433
Felix R M Koenig, Veronika Vetchy, Gregor Wollner, Maximilian Kern, Marcus Raudner, Veronika Janacova, Vladimir Juras, Pavol Szomolanyi, Markus M Schreiner, Siegfried Trattnig
{"title":"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.","authors":"Felix R M Koenig, Veronika Vetchy, Gregor Wollner, Maximilian Kern, Marcus Raudner, Veronika Janacova, Vladimir Juras, Pavol Szomolanyi, Markus M Schreiner, Siegfried Trattnig","doi":"10.1177/19476035251362433","DOIUrl":"10.1177/19476035251362433","url":null,"abstract":"<p><p>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 (<i>n</i> = 45). Patient-reported outcome measures (PROM) were assessed at all time points. Statistical tests included the Mann-Whitney <i>U</i>-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.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251362433"},"PeriodicalIF":2.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of Serum Biomarkers for Early-Stage Knee Osteoarthritis Using Proteomics in a Murine Model of Osteoarthritis. 利用蛋白质组学在小鼠骨关节炎模型中鉴定早期膝关节骨关节炎的血清生物标志物。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-08-08 DOI: 10.1177/19476035251363443
Shohei Yamauchi, Eiji Sasaki, Yota Tatara, Kyota Ishibashi, Takahiro Tsushima, Yuka Kimura, Eiichi Tsuda, Yasuyuki Ishibashi
{"title":"Identification of Serum Biomarkers for Early-Stage Knee Osteoarthritis Using Proteomics in a Murine Model of Osteoarthritis.","authors":"Shohei Yamauchi, Eiji Sasaki, Yota Tatara, Kyota Ishibashi, Takahiro Tsushima, Yuka Kimura, Eiichi Tsuda, Yasuyuki Ishibashi","doi":"10.1177/19476035251363443","DOIUrl":"10.1177/19476035251363443","url":null,"abstract":"<p><p>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, <i>P</i> = 0.03; 2.60 ± 1.71 points, <i>P</i> = 0.03) and 12 weeks after DMM (8.30 ± 3.12 points, <i>P</i> = 0.03; 4.80 ± 0.75 points, <i>P</i> = 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.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251363443"},"PeriodicalIF":2.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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. 磁共振成像衍生软骨形态改变及其与患者报告的骨性关节炎膝关节牵张后预后指标的相关性:一项为期12个月的队列研究。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-08-04 DOI: 10.1177/19476035251357836
Beth Lineham, Ahmad Joumah, Thomas Hamilton, Nagitha Wijayathunga, Hemant Pandit
{"title":"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.","authors":"Beth Lineham, Ahmad Joumah, Thomas Hamilton, Nagitha Wijayathunga, Hemant Pandit","doi":"10.1177/19476035251357836","DOIUrl":"10.1177/19476035251357836","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251357836"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
miR-708-5p Attenuates Osteoarthritis Progression via Multi-Target Modulation of the NOX4/NF-κB Axis and Cartilage Homeostasis. miR-708-5p通过多靶点调节NOX4/NF-κB轴和软骨稳态减缓骨关节炎进展。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-07-30 DOI: 10.1177/19476035251361679
Shih-Hao Huang, Zi Miao Liu, Shu-Jung Chen, Pin-Yi Tu, Yin-Chun Tien, Cheng-Chang Lu, Chih-Chien Wang, Li-Min Chen, Po-Chih Shen
{"title":"miR-708-5p Attenuates Osteoarthritis Progression via Multi-Target Modulation of the NOX4/NF-κB Axis and Cartilage Homeostasis.","authors":"Shih-Hao Huang, Zi Miao Liu, Shu-Jung Chen, Pin-Yi Tu, Yin-Chun Tien, Cheng-Chang Lu, Chih-Chien Wang, Li-Min Chen, Po-Chih Shen","doi":"10.1177/19476035251361679","DOIUrl":"10.1177/19476035251361679","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251361679"},"PeriodicalIF":2.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intra-articular Injections of Allogeneic Platelet-Rich Plasma from Responder Patients for the Treatment of Knee Osteoarthritis: A Pilot and Feasibility Clinical Trial. 来自应答患者的异体富血小板血浆关节内注射治疗膝骨关节炎:一项试点和可行性临床试验。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-07-29 DOI: 10.1177/19476035251355522
Mikel Sánchez, Jorge Guadilla, Cristina Jorquera, Daniel Marijuán-Pinel, Jon Mercader-Ruiz, Maider Beitia, Renato Andrade, João Espregueira-Mendes, Sergio González, Jaime Oraa, Leonor López de Dicastillo, Nicolás Fiz, Juan Azofra, Diego Delgado
{"title":"Intra-articular Injections of Allogeneic Platelet-Rich Plasma from Responder Patients for the Treatment of Knee Osteoarthritis: A Pilot and Feasibility Clinical Trial.","authors":"Mikel Sánchez, Jorge Guadilla, Cristina Jorquera, Daniel Marijuán-Pinel, Jon Mercader-Ruiz, Maider Beitia, Renato Andrade, João Espregueira-Mendes, Sergio González, Jaime Oraa, Leonor López de Dicastillo, Nicolás Fiz, Juan Azofra, Diego Delgado","doi":"10.1177/19476035251355522","DOIUrl":"10.1177/19476035251355522","url":null,"abstract":"<p><p>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 (<i>P</i> < .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 (<i>P</i> > .05) with a platelet concentration factor of 2.5. Donors were significantly younger than patients (<i>P</i> < .05) and presented higher levels of IGF-1 (<i>P</i> < .05). Cell bioactivity showed no differences between patient and donor PRP (<i>P</i> > .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.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251355522"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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. 微钻孔与微骨折治疗股骨远端软骨病变的mri观察软骨修复组织评分及功能结局的比较:回顾性比较研究。
IF 2.7 4区 医学
CARTILAGE Pub Date : 2025-07-29 DOI: 10.1177/19476035251360504
Junwoo Byun, Min Jung, Kwangho Chung, Hyun-Soo Moon, Se-Han Jung, Jin-Kyu Kim, Sung-Hwan Kim
{"title":"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.","authors":"Junwoo Byun, Min Jung, Kwangho Chung, Hyun-Soo Moon, Se-Han Jung, Jin-Kyu Kim, Sung-Hwan Kim","doi":"10.1177/19476035251360504","DOIUrl":"10.1177/19476035251360504","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035251360504"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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