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Back in Action: High Return to Pre-Injury Level of Sports after Arthroscopic Bone Marrow Stimulation for Osteochondral Lesions of the First Metatarsophalangeal (MTP-1) Joint. 重返赛场:关节镜下骨髓刺激治疗第一跖骨关节(MTP-1)骨软骨损伤后,运动恢复到伤前水平。
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-03-01 Epub Date: 2023-09-21 DOI: 10.1177/19476035231200332
Carlijn S Ter Laak Bolk, Quinten G H Rikken, Jari Dahmen, Yoshiharu Shimozono, Masato Takao, Sjoerd A S Stufkens, Gino M M J Kerkhoffs

Objective: The primary aim was to assess the return to sports outcomes of patients with symptomatic osteochondral lesions (OCLs) to the first metatarsophalangeal (MTP-1) joint treated by arthroscopic bone marrow stimulation (BMS). Secondary aims were to present patient-reported outcome measures (PROMs) on pain scores as well as surgery-related complications or reoperations to the MTP-1 joint.

Design: All patients with MTP-1 OCLs treated by arthroscopic BMS with a minimum follow-up of 12 months were included. Outcomes included return to sports and work outcomes, satisfaction outcomes with the performed treatment, PROMs, as well as postoperative complications and reoperations. Medical records were screened by 2 independent reviewers and patients were contacted by phone to partake in an in-depth interview. Complications, reoperations, and revision surgeries were additionally assessed.

Results: Nine patients (median age: 22 years with interquartile range (IQR) 20-29 years) were included with a median follow-up time of 47 (IQR: 23-92) months. Six (86%) out of 7 patients who participated in sports preoperatively returned to sports at any level at a median of 4 (IQR: 2.6-5.8) months. Five patients (71%) returned to pre-injury level of sport and eventually returned to performance at a median of 4 (IQR 2.8-7.5) and 8 (IQR: 4.0-10.5) months, respectively. The median Numeric Rating Scale for pain during walking was 1 (IQR 0-2.5) and all (100%) patients were able to return to work at a median of 4 (IQR: 2-17) weeks. Eighty-nine percent of the patients were very or fairly satisfied with the result of their treatment. No complications, reoperations, or revision surgeries were reported.

Conclusions: Arthroscopic BMS for patients with symptomatic OCLs to the MTP-1 joint can be considered safe and yields an 86% return to sport at any level and a 71% return to pre-injury and performance level, with good clinical, return to work, as well as satisfaction outcomes.

目的:主要目的是评估关节镜下骨髓刺激(BMS)治疗第一跖趾(MTP-1)关节症状性骨软骨损伤(OCL)患者恢复运动的效果。次要目的是介绍患者报告的疼痛评分以及MTP-1关节手术相关并发症或再次手术的结果测量(PROM)。设计:所有MTP-1 OCL患者均接受关节镜下BMS治疗,随访时间至少为12个月。结果包括恢复运动和工作的结果、对所进行治疗的满意度结果、胎膜早破、术后并发症和再次手术。两名独立评审员对医疗记录进行了筛选,并通过电话联系患者进行深入访谈。对并发症、再次手术和翻修手术进行了额外评估。结果:纳入9名患者(中位年龄:22岁,四分位间距(IQR)20-29岁),中位随访时间为47个月(IQR:23-92)。术前参加运动的7名患者中有6名(86%)在中位4个月(IQR:2.6-5.8)后恢复了任何水平的运动。5名患者(71%)恢复到受伤前的运动水平,并最终分别在中位数为4个月(IQR 2.8-7.5)和8个月(IQ R:4.0-10.5)时恢复到运动水平。行走过程中疼痛的中位数字评定量表为1(IQR 0-2.5),所有(100%)患者都能在中位4周(IQR:2-17)后重返工作岗位。89%的患者对他们的治疗结果非常或相当满意。没有并发症、再次手术或翻修手术的报告。结论:对于MTP-1关节有症状的OCL患者,关节镜下BMS可以被认为是安全的,在任何水平上都可以恢复86%的运动,恢复71%的损伤前和表现水平,具有良好的临床、恢复工作和满意的结果。
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引用次数: 0
HSF1 Increases EOGT-Mediated Glycosylation of Notch1 to Promote IL-1β-Induced Inflammatory Injury of Chondrocytes. HSF1 可增加 EOGT 介导的 Notch1 糖基化,从而促进 IL-1β 诱导的软骨细胞炎症损伤。
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-02-16 DOI: 10.1177/19476035241229211
Yuanchi Huang, Wenjie Pan, Huanli Bao, Xiangxiang Sun, Chao Xu, Jianbing Ma

Objective: Osteoarthritis (OA) is the most common arthritic disease in humans. Nevertheless, the pathogenic mechanism of OA remains unclear. This study aimed to explore that heat-shock transcription factor 1 (HSF1) facilitated interleukin-1 beta (IL-1β) chondrocyte injury by increasing Notch1 O-linked N-acetylglucosamine (O-GlcNAc) modification level.

Design: Human chondrocytes were incubated with 5 ng/ml interleukin-1 beta (IL-1β) for 24 h to establish OA cell model. The messenger RNA (mRNA) or protein expressions were assessed using reverse transcription-quantitative polymerase chain reaction, western blot, or immunofluorescence. Chondrocyte viability was examined by Cell Counting Kit-8 assay. Enzyme-linked immunosorbent assay was employed to detect the secretion levels of interleukin-6 (IL-6) and interleukin-8 (IL-8). Immunoprecipitation was adopted to detect Notch1 O-GlcNAc modification level. The interaction between HSF1 and epidermal growth factor-like (EGF) domain-specific O-GlcNAc transferase (EOGT) promoter was analyzed by dual-luciferase reporter gene and chromatin immunoprecipitation assays.

Results: Herein, our results demonstrated that HSF1, EOGT, Notch1, and Notch1 intracellular domain (NICD1) expressions in chondrocytes were markedly increased by IL-1β stimulation. EOGT elevated Notch1 expression in IL-1β-treated chondrocytes by increasing Notch1 O-GlcNAc modification level. EOGT silencing reduced IL-1β-induced chondrocyte inflammatory injury. In addition, HSF1 knockdown relieved IL-1β-induced chondrocyte inflammatory injury. Molecular interaction experiment proved that HSF1 transcriptionally activated EOGT expression in IL-1β-treated chondrocytes.

Conclusions: HSF1 promoted IL-1β-induced inflammatory injury in chondrocytes by increasing EOGT-mediated glycosylation of Notch1.

目的:骨关节炎(OA)是人类最常见的关节炎疾病:骨关节炎(OA)是人类最常见的关节炎疾病。然而,OA 的致病机制仍不清楚。本研究旨在探讨热休克转录因子1(HSF1)通过增加Notch1 O-连接的N-乙酰葡糖胺(O-GlcNAc)修饰水平促进白细胞介素-1β(IL-1β)软骨细胞损伤:设计:将人软骨细胞与 5 ng/ml 的白细胞介素-1β(IL-1β)培养 24 小时,以建立 OA 细胞模型。用逆转录-定量聚合酶链反应、Western 印迹或免疫荧光法评估信使 RNA(mRNA)或蛋白质的表达。用细胞计数试剂盒-8检测软骨细胞的活力。酶联免疫吸附法检测白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的分泌水平。免疫沉淀法检测 Notch1 O-GlcNAc 修饰水平。通过双荧光素酶报告基因和染色质免疫沉淀实验分析了HSF1与表皮生长因子样(EGF)结构域特异性O-GlcNAc转移酶(EOGT)启动子之间的相互作用:结果:我们的研究结果表明,HSF1、EOGT、Notch1和Notch1胞内结构域(NICD1)在软骨细胞中的表达在IL-1β刺激下显著增加。EOGT通过增加Notch1 O-GlcNAc修饰水平提高了Notch1在IL-1β处理的软骨细胞中的表达。沉默EOGT可减少IL-1β诱导的软骨细胞炎症损伤。此外,HSF1敲除可缓解IL-1β诱导的软骨细胞炎症损伤。分子相互作用实验证明,HSF1转录激活了IL-1β处理的软骨细胞中EOGT的表达:结论:HSF1通过增加EOGT介导的Notch1糖基化促进了IL-1β诱导的软骨细胞炎症损伤。
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引用次数: 0
Reporting of Morphology, Location, and Size in the Treatment of Osteochondral Lesions of the Talus in 11,785 Patients: A Systematic Review and Meta-Analysis. 对 11,785 例距骨软骨病变治疗中形态、位置和大小的报告:系统回顾与元分析》。
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-02-16 DOI: 10.1177/19476035241229026
Pascal R van Diepen, Frank F Smithuis, Julian J Hollander, Jari Dahmen, Kaj S Emanuel, Sjoerd A S Stufkens, Gino M M J Kerkhoffs

Objective: Uniformity of reporting is a requisite to be able to compare results of clinical studies on the treatment of osteochondral lesions of the talus (OLT). The primary aim of this study was to evaluate the frequency and quality of reporting of size, morphology, and location of OLTs.

Design: A literature search was performed from 1996 to 2023 to identify clinical studies on surgical treatment of OLTs. Screening was performed by 2 reviewers, who subsequently graded the quality using the methodological index for non-randomized studies (MINORS). The primary outcome was the frequency and qualitative assessment of reporting of size, morphology, and location.

Results: Of 3,074 articles, 262 articles were included. This comprised a total of 11,785 patients. Size was reported in 248 (95%) of the articles and was described with a measure for surface area in 83%, however, in 56%, definition of measurement is unknown. Intraclass coefficient (ICC) value for the reliability of size measurement was 0.94 for computed tomography (CT) scan and 0.87 for MRI scan. Morphology was reported in 172 (66%) of the articles and using a classification system in 23% of the studies. Location was reported in 220 (84%) of the studies.

Conclusion: No consensus was found on the reporting of morphology, with non-validated classification systems and different terminologies used. For location, reporting in 9 zones is underreported. Size was well reported and measurements are more reliable for CT compared with MRI. As these prognostic factors guide clinical decision-making, we advocate the development of a standardized and validated OLT classification to reach uniform reporting in literature.

Level of evidence: Level III, systematic review.

目的:要比较治疗距骨骨软骨损伤(OLT)的临床研究结果,报告的统一性是必要条件。本研究的主要目的是评估有关 OLTs 大小、形态和位置的报告频率和质量:设计:对1996年至2023年的文献进行检索,以确定有关OLT手术治疗的临床研究。由两名审稿人进行筛选,然后使用非随机研究的方法学指数(MINORS)进行质量分级。主要结果是报告大小、形态和位置的频率和定性评估:结果:在 3074 篇文章中,有 262 篇被纳入。结果:在 3,074 篇文章中,有 262 篇文章被收录,共包括 11,785 名患者。248篇文章(95%)报告了肿瘤的大小,83%的文章用表面积来描述,但56%的文章测量定义不明。计算机断层扫描(CT)和核磁共振成像(MRI)扫描的尺寸测量可靠性的类内系数(ICC)分别为 0.94 和 0.87。172篇文章(66%)报告了形态,23%的研究使用了分类系统。220篇(84%)研究报告了位置:结论:在形态学报告方面没有达成共识,分类系统未经验证,使用的术语也不尽相同。关于位置,9 个区域的报告不足。对大小的报告较多,CT 与 MRI 相比,测量结果更可靠。由于这些预后因素对临床决策有指导作用,我们主张制定一个标准化的、经过验证的OLT分类,以实现文献报告的统一:证据等级:III级,系统综述。
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引用次数: 0
Cellular Enhancement of Frozen Meniscus Allograft Combining Native Meniscus and Mesenchymal Stromal Cell Injections. 结合原生半月板和间充质基质细胞注射的冷冻半月板异体移植的细胞强化作用
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-02-07 DOI: 10.1177/19476035231224802
Caroline Struijk, Katherine L Lydon, Martin Husen, Peter Verdonk, Jozef Michielsen, Andre J van Wijnen, Aaron J Krych, Daniel B F Saris

Objective: This proof-of-concept study investigated an improved cell-based injection therapy combining mesenchymal stem cells (MSCs) and meniscus cells (MCs) to support superior meniscus allograft repopulation and early revival compared to injecting MSCs alone.

Design: In this controlled laboratory study, frozen meniscus allograft samples were injected vertically with a cell suspension containing different ratios of MSCs and MCs or control (lactated ringers) and cultured for 28 days. Samples were analyzed weekly for cell viability, migration, and metabolism using histological and biochemical assays. Tissue medium was analyzed for matrix metalloproteinase (MMP) expression using zymography.

Results: Cellular repopulation of frozen allografts injected with different cell suspensions was validated by immunohistochemistry. Significant higher DNA content was evidenced in grafts treated with suspensions of MCs or MC:MSC (1:4 ratio). Cell metabolic activity was significantly different between all treated groups and control group after 1 week. Allografts injected with MCs showed significantly more cell proliferation than injections with MSCs. MMP2 activity was detected in medium of all grafts cellularized with MCs with or without MSCs. Scanning electron microscopy (SEM) analysis showed resolution of the needle puncture, but not in the control group. Cell labeling of MCs upon injection of mixed MC:MSC suspensions revealed a gradual increase in the cell ratio.

Conclusions: The findings of this study establish that injection of MCs with or without MSCs enhances the cellularity of meniscus allograft to support early graft revival and remodeling.

目的:这项概念验证研究调查了一种改进的基于细胞的注射疗法,该疗法结合了间充质干细胞(MSCs)和半月板细胞(MCs),与单独注射间充质干细胞相比,它能支持半月板异体移植物的良好再填充和早期复苏:在这项实验室对照研究中,将冷冻的半月板异体移植物样本垂直注入含有不同比例间充质干细胞和MC或对照组(乳化环状细胞)的细胞悬液,并培养28天。每周使用组织学和生化分析法对样本进行细胞活力、迁移和新陈代谢分析。使用酶谱分析法分析组织介质中基质金属蛋白酶(MMP)的表达:结果:免疫组化验证了注射不同细胞悬浮液的冷冻异体移植物的细胞再填充。使用 MCs 或 MC:MSC(1:4 比例)悬浮液处理的移植物 DNA 含量明显更高。一周后,所有处理组与对照组的细胞代谢活性均有明显差异。注射 MCs 的异体移植物的细胞增殖明显多于注射间充质干细胞的异体移植物。在所有使用或不使用间充质干细胞的MCs细胞化移植物的培养基中都检测到了MMP2活性。扫描电子显微镜(SEM)分析表明针头穿刺的分辨率,而对照组则没有。注射 MC:MSC 混合悬浮液后,MCs 的细胞标记显示细胞比例逐渐增加:本研究结果表明,注射含有或不含间叶干细胞的 MCs 可增强半月板异体移植的细胞性,从而支持移植的早期恢复和重塑。
{"title":"Cellular Enhancement of Frozen Meniscus Allograft Combining Native Meniscus and Mesenchymal Stromal Cell Injections.","authors":"Caroline Struijk, Katherine L Lydon, Martin Husen, Peter Verdonk, Jozef Michielsen, Andre J van Wijnen, Aaron J Krych, Daniel B F Saris","doi":"10.1177/19476035231224802","DOIUrl":"https://doi.org/10.1177/19476035231224802","url":null,"abstract":"<p><strong>Objective: </strong>This proof-of-concept study investigated an improved cell-based injection therapy combining mesenchymal stem cells (MSCs) and meniscus cells (MCs) to support superior meniscus allograft repopulation and early revival compared to injecting MSCs alone.</p><p><strong>Design: </strong>In this controlled laboratory study, frozen meniscus allograft samples were injected vertically with a cell suspension containing different ratios of MSCs and MCs or control (lactated ringers) and cultured for 28 days. Samples were analyzed weekly for cell viability, migration, and metabolism using histological and biochemical assays. Tissue medium was analyzed for matrix metalloproteinase (MMP) expression using zymography.</p><p><strong>Results: </strong>Cellular repopulation of frozen allografts injected with different cell suspensions was validated by immunohistochemistry. Significant higher DNA content was evidenced in grafts treated with suspensions of MCs or MC:MSC (1:4 ratio). Cell metabolic activity was significantly different between all treated groups and control group after 1 week. Allografts injected with MCs showed significantly more cell proliferation than injections with MSCs. MMP2 activity was detected in medium of all grafts cellularized with MCs with or without MSCs. Scanning electron microscopy (SEM) analysis showed resolution of the needle puncture, but not in the control group. Cell labeling of MCs upon injection of mixed MC:MSC suspensions revealed a gradual increase in the cell ratio.</p><p><strong>Conclusions: </strong>The findings of this study establish that injection of MCs with or without MSCs enhances the cellularity of meniscus allograft to support early graft revival and remodeling.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Second-Look Arthroscopy Shows Inferior Cartilage after Bone Marrow Stimulation Compared with Other Operative Techniques for Osteochondral Lesions of the Talus: A Systematic Review and Meta-Analysis. 与其他治疗距骨骨软骨损伤的手术技术相比,第二眼关节镜检查显示骨髓刺激术后软骨较差:系统回顾与元分析。
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-02-07 DOI: 10.1177/19476035241227332
Jelmer T Vreeken, Jari Dahmen, Tobias Stornebrink, Kaj S Emanuel, Alex B Walinga, Sjoerd A S Stufkens, Gino M M J Kerkhoffs

Objective: To compare cartilage quality after different surgical interventions for osteochondral lesions of the talus (OLT), evaluated by second-look arthroscopy. Secondary aims were to report concomitant diagnoses, and to correlate cartilage quality with clinical and radiological outcomes. This review hypothesizes that the cartilage repair after bone marrow stimulation (BMS) is inferior to the other available treatment options.

Methods: PROSPERO ID: CRD42022311489. Studies were retrieved through PubMed, EMBASE (Ovid), and Cochrane Library. Studies were included if they reported cartilage quality after second-look investigation after surgical treatment of OLT. The primary outcome measure was the cartilage quality success and failure rates (%) per surgical intervention group. Correlations between the cartilage quality and clinical or radiological outcomes were calculated.

Results: Twenty-nine studies were included, comprising 586 ankles that had undergone second-look arthroscopy on average 16 months after initial surgery. The success rate for BMS was 57% (95% confidence interval [CI] = 48%-65%), for fixation (FIX) 86% (95% CI = 70%-94%), for osteo(chondral) transplantation (OCT) 91% (95% CI = 80%-96%), for cartilage implementation techniques (CITs) 80% (95% CI = 69%-88%), and for retrograde drilling 100% (95% CI = 66%-100%). The success rate of BMS was significantly lower than FIX, OCT, and CIT (P < 0.01). There were no significant differences between other treatment groups. A moderate positive significant correlation between the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and the International Cartilage Repair Society score (ICRS) was found (ρ = 0.51, P < 0.001).

Conclusions: Successful restoration of cartilage quality was found in the majority of surgically treated OLTs. However, BMS yields inferior cartilage quality compared with FIX, OCT, and CIT. Study Design. Systematic review and meta-analysis. Level of evidence. Level IV, systematic review and meta-analysis.

目的通过关节镜二视图评估,比较不同手术干预治疗距骨软骨损伤(OLT)后的软骨质量。次要目的是报告伴随诊断,并将软骨质量与临床和放射学结果相关联。本综述假设骨髓刺激(BMS)后的软骨修复效果不如其他可用的治疗方案:PROSPERO ID:CRD42022311489。通过 PubMed、EMBASE (Ovid) 和 Cochrane Library 检索研究。如果研究报告了OLT手术治疗后进行二诊检查后的软骨质量,则纳入该研究。主要结果指标是每个手术干预组的软骨质量成功率和失败率(%)。计算软骨质量与临床或放射学结果之间的相关性:共纳入29项研究,包括586个脚踝,这些脚踝在初次手术后平均16个月接受了二次关节镜检查。BMS的成功率为57%(95%置信区间[CI] = 48%-65%),固定术(FIX)的成功率为86%(95% CI = 70%-94%),骨(软骨)移植术(OCT)的成功率为91%(95% CI = 80%-96%),软骨植入技术(CIT)的成功率为80%(95% CI = 69%-88%),逆行钻孔术的成功率为100%(95% CI = 66%-100%)。BMS的成功率明显低于FIX、OCT和CIT(P < 0.01)。其他治疗组之间无明显差异。结论:软骨修复组织磁共振观察(MOCART)评分与国际软骨修复协会评分(ICRS)呈中度正相关(ρ = 0.51,P < 0.001):结论:大多数经手术治疗的 OLT 都能成功恢复软骨质量。然而,与 FIX、OCT 和 CIT 相比,BMS 的软骨质量较差。研究设计。系统回顾和荟萃分析。证据级别。IV级,系统回顾和荟萃分析。
{"title":"Second-Look Arthroscopy Shows Inferior Cartilage after Bone Marrow Stimulation Compared with Other Operative Techniques for Osteochondral Lesions of the Talus: A Systematic Review and Meta-Analysis.","authors":"Jelmer T Vreeken, Jari Dahmen, Tobias Stornebrink, Kaj S Emanuel, Alex B Walinga, Sjoerd A S Stufkens, Gino M M J Kerkhoffs","doi":"10.1177/19476035241227332","DOIUrl":"https://doi.org/10.1177/19476035241227332","url":null,"abstract":"<p><strong>Objective: </strong>To compare cartilage quality after different surgical interventions for osteochondral lesions of the talus (OLT), evaluated by second-look arthroscopy. Secondary aims were to report concomitant diagnoses, and to correlate cartilage quality with clinical and radiological outcomes. This review hypothesizes that the cartilage repair after bone marrow stimulation (BMS) is inferior to the other available treatment options.</p><p><strong>Methods: </strong>PROSPERO ID: CRD42022311489. Studies were retrieved through PubMed, EMBASE (Ovid), and Cochrane Library. Studies were included if they reported cartilage quality after second-look investigation after surgical treatment of OLT. The primary outcome measure was the cartilage quality success and failure rates (%) per surgical intervention group. Correlations between the cartilage quality and clinical or radiological outcomes were calculated.</p><p><strong>Results: </strong>Twenty-nine studies were included, comprising 586 ankles that had undergone second-look arthroscopy on average 16 months after initial surgery. The success rate for BMS was 57% (95% confidence interval [CI] = 48%-65%), for fixation (FIX) 86% (95% CI = 70%-94%), for osteo(chondral) transplantation (OCT) 91% (95% CI = 80%-96%), for cartilage implementation techniques (CITs) 80% (95% CI = 69%-88%), and for retrograde drilling 100% (95% CI = 66%-100%). The success rate of BMS was significantly lower than FIX, OCT, and CIT (<i>P</i> < 0.01). There were no significant differences between other treatment groups. A moderate positive significant correlation between the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and the International Cartilage Repair Society score (ICRS) was found (ρ = 0.51, <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Successful restoration of cartilage quality was found in the majority of surgically treated OLTs. However, BMS yields inferior cartilage quality compared with FIX, OCT, and CIT. <i>Study Design.</i> Systematic review and meta-analysis. <i>Level of evidence.</i> Level IV, systematic review and meta-analysis.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Diclofenac Etalhyaluronate (SI-613/ONO-5704) on Cartilage Degeneration in Arthritic Rats and Inflammatory Cytokine-Stimulated Human Chondrocytes. 双氯芬酸乙醛脲酸酯(SI-613/ONO-5704)对关节炎大鼠软骨退变和炎性细胞因子刺激人软骨细胞的影响
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-02-05 DOI: 10.1177/19476035231224050
Shuhei Takada, Risa Nodera, Keiji Yoshioka

Objective: Cartilage degeneration is a key feature of osteoarthritis (OA) and rheumatoid arthritis and is thought to negatively impact patients' quality of life. Diclofenac etalhyaluronate (DEH, SI-613/ONO-5704) is a hyaluronic acid (HA) derivative chemically bound to diclofenac (DF) that has been reported to improve OA symptoms; however, its effect on cartilage degeneration remains unknown. In the present study, we investigated the chondroprotective effect of DEH in rats with collagen-induced arthritis and interleukin-1β-stimulated human chondrocytes.

Design: Rats with collagen-induced arthritis were administered DEH and HA intra-articularly, and DF orally. Knee joint swelling, histological scores of articular cartilage, and inflammatory (Il1b) and catabolic (Mmp3 and Mmp13) gene expression in the synovial tissue and cartilage were evaluated. In vitro direct effects of DEH on matrix metalloproteinase (MMP)-3 and MMP-13 expression were examined in interleukin-1β-stimulated human chondrocytes.

Results: In a rat model of collagen-induced arthritis, a single intra-articular dose of DEH inhibited knee joint inflammation and cartilage degeneration. Daily oral administration of DF had similar effects. Conversely, HA administered as a single intra-articular dose had no effect. Only DEH inhibited Mmp3 gene expression in the cartilage, whereas DEH and DF inhibited Mmp3 and Mmp13 mRNA expression in the synovial tissue. In interleukin-1β-stimulated human chondrocytes, DEH and HA inhibited MMP-3 and MMP-13 production, whereas DF had no effect.

Conclusions: In this study, we demonstrated the chondroprotective effect of DEH in rats with collagen-induced arthritis and in interleukin-1β-stimulated human chondrocytes. Thus, DEH may suppress cartilage degeneration in patients with musculoskeletal diseases, such as OA.

目的:软骨退化是骨关节炎(OA)和类风湿性关节炎的主要特征,被认为会对患者的生活质量产生负面影响。双氯芬酸乙醛脲酸酯(DEH,SI-613/ONO-5704)是一种与双氯芬酸(DF)化学结合的透明质酸(HA)衍生物,有报道称它能改善 OA 症状;然而,它对软骨退化的影响仍然未知。在本研究中,我们研究了DEH对胶原诱导的关节炎大鼠和白细胞介素-1β刺激的人类软骨细胞的软骨保护作用:设计:给胶原蛋白诱导的关节炎大鼠关节内注射DEH和HA,口服DF。对膝关节肿胀、关节软骨组织学评分、滑膜组织和软骨中炎症(Il1b)和分解(Mmp3 和 Mmp13)基因表达进行评估。体外研究了白细胞介素-1β刺激的人软骨细胞中 DEH 对基质金属蛋白酶(MMP)-3 和 MMP-13 表达的直接影响:结果:在胶原蛋白诱导的大鼠关节炎模型中,单次关节内注射 DEH 可抑制膝关节炎症和软骨退化。每日口服 DF 也有类似效果。相反,单次关节内给药的 HA 则没有效果。只有 DEH 抑制了软骨中 Mmp3 基因的表达,而 DEH 和 DF 则抑制了滑膜组织中 Mmp3 和 Mmp13 mRNA 的表达。在白细胞介素-1β刺激的人软骨细胞中,DEH和HA抑制了MMP-3和MMP-13的产生,而DF则没有影响:在这项研究中,我们证实了 DEH 对胶原诱导的关节炎大鼠和白细胞介素-1β刺激的人类软骨细胞具有软骨保护作用。因此,DEH 可抑制肌肉骨骼疾病(如 OA)患者的软骨退化。
{"title":"Effects of Diclofenac Etalhyaluronate (SI-613/ONO-5704) on Cartilage Degeneration in Arthritic Rats and Inflammatory Cytokine-Stimulated Human Chondrocytes.","authors":"Shuhei Takada, Risa Nodera, Keiji Yoshioka","doi":"10.1177/19476035231224050","DOIUrl":"https://doi.org/10.1177/19476035231224050","url":null,"abstract":"<p><strong>Objective: </strong>Cartilage degeneration is a key feature of osteoarthritis (OA) and rheumatoid arthritis and is thought to negatively impact patients' quality of life. Diclofenac etalhyaluronate (DEH, SI-613/ONO-5704) is a hyaluronic acid (HA) derivative chemically bound to diclofenac (DF) that has been reported to improve OA symptoms; however, its effect on cartilage degeneration remains unknown. In the present study, we investigated the chondroprotective effect of DEH in rats with collagen-induced arthritis and interleukin-1β-stimulated human chondrocytes.</p><p><strong>Design: </strong>Rats with collagen-induced arthritis were administered DEH and HA intra-articularly, and DF orally. Knee joint swelling, histological scores of articular cartilage, and inflammatory (Il1b) and catabolic (Mmp3 and Mmp13) gene expression in the synovial tissue and cartilage were evaluated. In vitro direct effects of DEH on matrix metalloproteinase (MMP)-3 and MMP-13 expression were examined in interleukin-1β-stimulated human chondrocytes.</p><p><strong>Results: </strong>In a rat model of collagen-induced arthritis, a single intra-articular dose of DEH inhibited knee joint inflammation and cartilage degeneration. Daily oral administration of DF had similar effects. Conversely, HA administered as a single intra-articular dose had no effect. Only DEH inhibited Mmp3 gene expression in the cartilage, whereas DEH and DF inhibited Mmp3 and Mmp13 mRNA expression in the synovial tissue. In interleukin-1β-stimulated human chondrocytes, DEH and HA inhibited MMP-3 and MMP-13 production, whereas DF had no effect.</p><p><strong>Conclusions: </strong>In this study, we demonstrated the chondroprotective effect of DEH in rats with collagen-induced arthritis and in interleukin-1β-stimulated human chondrocytes. Thus, DEH may suppress cartilage degeneration in patients with musculoskeletal diseases, such as OA.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Higher Age is Associated with Lower Likelihood of Conversion to Surgery after Primary Nonoperative Treatment for Osteochondral Lesions of the Talus. 年龄越大,距骨骨软骨损伤初级非手术治疗后转为手术治疗的可能性越低。
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2024-01-26 DOI: 10.1177/19476035241227357
Tristan M F Buck, Jari Dahmen, J Nienke Altink, Quinten G H Rikken, Inger N Sierevelt, Sjoerd A S Stufkens, Gino M M J Kerkhoffs

Introduction: The first line of treatment for osteochondral lesions of the talus (OLT) is nonoperative. To date, there is limited evidence on risk factors that may influence conversion to surgery after primary nonoperative treatment for symptomatic OLTs. The aim of this study was therefore to identify risk factors for conversion to surgery after initial nonoperative treatment of OLTs.

Methods: For this cohort study, patients with a primary OLT who were nonoperatively treated for at least 6 months between 1990 and 2020 were included. Univariable Cox regression analysis, resulting in hazard ratios (HRs), on the primary outcome (i.e. conversion to surgery after initial nonoperative treatment) was performed for potential risk factors. The following risk factors were analyzed: gender, age, body mass index (BMI), numeric rating scale (NRS), lesion size (depth, sagittal length, coronal length, volume, surface), lesion morphology (presence of fragments and presence of cysts), lesion location (medial/central/lateral), congruency of the ankle joint and trauma in history. Data imputation was conducted according to the multiple data principle with pooling.

Results: Forty-two patients with primary OLTs were included in this study: 23 (55%) males and 19 (45%) females with a mean age of 39.1 (SD: 14.2). The median overall follow-up time was 66 months (range: 7-188). Around 23% of the patients had a conversion to surgery at the median observation time. The Kaplan-Meier analysis revealed a survival rate of 93% (95% confidence interval [CI]:84-100), 90% (95% CI: 81-99), and 77% (95% CI: 63-91) at 1, 2, and 5 years after the initiation of treatment, respectively. After performing the COX regression analysis, age was the sole risk factor significantly associated with conversion to surgery with an HR of 0.93 (95% CI: 0.87-0.99). The different HRs for all other risk factors were as follows: gender: 0.33 (95% CI: 0.08-1.34), BMI: 0.87 (95% CI 0.76-1.01), depth: 0.97 (95% CI: 0.79-1.18), coronal length: 1.19 (95% CI: 0.97-1.44), sagittal length: 0.98 (95% CI: 0.87-1.12), surface area: 1.17 (95% CI: 0.41-3.31), volume: 0.96 (95% CI: 0.24-3.91), presence of fragments: 4.17 (95% CI: 0.84-20.61).

Conclusion: For primary OLTs, 77% of the patients were successfully treated nonoperatively at a median follow-up of 66 months without the need for a surgical intervention. Survival rates of 93%, 90%, and 77% were found at 1, 2, and 5 years after the initiation of treatment, respectively. We found that a higher age at the moment of diagnosis was significantly associated with a lower likelihood of conversion to surgery with a 7% decrease of likelihood each year the patient is older at the moment of diagnosis. The findings of this study are clinically relevant as it ameliorates the quality of the shared decision-making process between the patient and the treating team as we can advise OLT patients

简介:距骨骨软骨损伤(OLT)的一线治疗方法是非手术治疗。迄今为止,关于影响无症状 OLT 初级非手术治疗后转为手术治疗的风险因素的证据还很有限。因此,本研究旨在确定OLTs初次非手术治疗后转为手术治疗的风险因素:在这项队列研究中,纳入了 1990 年至 2020 年间接受过至少 6 个月非手术治疗的原发性 OLT 患者。针对潜在风险因素进行了单变量考克斯回归分析,得出了主要结果(即初始非手术治疗后转为手术治疗)的危险比(HRs)。分析了以下风险因素:性别、年龄、体重指数(BMI)、数字评分量表(NRS)、病变大小(深度、矢状线长度、冠状线长度、体积、表面)、病变形态(是否存在碎片和囊肿)、病变位置(内侧/中央/外侧)、踝关节的一致性和外伤史。根据多数据原则进行数据归类,并进行汇总:本研究共纳入42例原发性OLT患者:其中男性23例(55%),女性19例(45%),平均年龄39.1岁(标清:14.2岁)。中位随访时间为 66 个月(7-188 个月)。在中位观察时间内,约有 23% 的患者转为手术治疗。卡普兰-梅耶尔分析显示,治疗开始后 1 年、2 年和 5 年的生存率分别为 93%(95% 置信区间[CI]:84-100)、90%(95% CI:81-99)和 77%(95% CI:63-91)。在进行 COX 回归分析后,年龄是与转为手术显著相关的唯一风险因素,HR 值为 0.93(95% CI:0.87-0.99)。所有其他风险因素的不同 HR 值如下:性别:0.33(95% CI:0.08-1.34),BMI:0.87(95% CI:0.76-1.01),深度:0.97(95% CI:0.79-1.18),冠状长度:1.19(95% CI:0.97-1.44),矢状长度:0.98(95% CI:0.87-1.12),表面积:1.17(95% CI:0.87-1.44),髂骨长度:0.87(95% CI:0.76-1.01),髂骨长度:0.87(95% CI:0.76-1.01):1.17(95% CI:0.41-3.31),体积:0.96(95% CI:0.24-3.91),是否有碎片:4.17 (95% CI: 0.84-20.61):对于原发性 OLT,77% 的患者在中位随访 66 个月后成功接受了非手术治疗,无需手术干预。治疗开始后 1 年、2 年和 5 年的存活率分别为 93%、90% 和 77%。我们发现,确诊时年龄越大,转为手术治疗的可能性就越低,而且年龄越大,转为手术治疗的可能性每年降低 7%。这项研究的结果与临床相关,因为它改善了患者与治疗团队之间共同决策过程的质量,因为我们可以告知症状可耐受的高龄 OLT 患者,转为手术治疗的风险相对较低。
{"title":"Higher Age is Associated with Lower Likelihood of Conversion to Surgery after Primary Nonoperative Treatment for Osteochondral Lesions of the Talus.","authors":"Tristan M F Buck, Jari Dahmen, J Nienke Altink, Quinten G H Rikken, Inger N Sierevelt, Sjoerd A S Stufkens, Gino M M J Kerkhoffs","doi":"10.1177/19476035241227357","DOIUrl":"https://doi.org/10.1177/19476035241227357","url":null,"abstract":"<p><strong>Introduction: </strong>The first line of treatment for osteochondral lesions of the talus (OLT) is nonoperative. To date, there is limited evidence on risk factors that may influence conversion to surgery after primary nonoperative treatment for symptomatic OLTs. The aim of this study was therefore to identify risk factors for conversion to surgery after initial nonoperative treatment of OLTs.</p><p><strong>Methods: </strong>For this cohort study, patients with a primary OLT who were nonoperatively treated for at least 6 months between 1990 and 2020 were included. Univariable Cox regression analysis, resulting in hazard ratios (HRs), on the primary outcome (i.e. conversion to surgery after initial nonoperative treatment) was performed for potential risk factors. The following risk factors were analyzed: gender, age, body mass index (BMI), numeric rating scale (NRS), lesion size (depth, sagittal length, coronal length, volume, surface), lesion morphology (presence of fragments and presence of cysts), lesion location (medial/central/lateral), congruency of the ankle joint and trauma in history. Data imputation was conducted according to the multiple data principle with pooling.</p><p><strong>Results: </strong>Forty-two patients with primary OLTs were included in this study: 23 (55%) males and 19 (45%) females with a mean age of 39.1 (SD: 14.2). The median overall follow-up time was 66 months (range: 7-188). Around 23% of the patients had a conversion to surgery at the median observation time. The Kaplan-Meier analysis revealed a survival rate of 93% (95% confidence interval [CI]:84-100), 90% (95% CI: 81-99), and 77% (95% CI: 63-91) at 1, 2, and 5 years after the initiation of treatment, respectively. After performing the COX regression analysis, age was the sole risk factor significantly associated with conversion to surgery with an HR of 0.93 (95% CI: 0.87-0.99). The different HRs for all other risk factors were as follows: gender: 0.33 (95% CI: 0.08-1.34), BMI: 0.87 (95% CI 0.76-1.01), depth: 0.97 (95% CI: 0.79-1.18), coronal length: 1.19 (95% CI: 0.97-1.44), sagittal length: 0.98 (95% CI: 0.87-1.12), surface area: 1.17 (95% CI: 0.41-3.31), volume: 0.96 (95% CI: 0.24-3.91), presence of fragments: 4.17 (95% CI: 0.84-20.61).</p><p><strong>Conclusion: </strong>For primary OLTs, 77% of the patients were successfully treated nonoperatively at a median follow-up of 66 months without the need for a surgical intervention. Survival rates of 93%, 90%, and 77% were found at 1, 2, and 5 years after the initiation of treatment, respectively. We found that a higher age at the moment of diagnosis was significantly associated with a lower likelihood of conversion to surgery with a 7% decrease of likelihood each year the patient is older at the moment of diagnosis. The findings of this study are clinically relevant as it ameliorates the quality of the shared decision-making process between the patient and the treating team as we can advise OLT patients","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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 Q1 ORTHOPEDICS Pub 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

Objective: The 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 in vitro. 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 methods: A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed.

Results: PRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling.

Conclusion: Actin-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 in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.

目的:关节软骨表层区(SZ)负责分散剪切力,使软骨负荷达到最佳状态,并通过产生蛋白多糖 4(PRG4)促进关节润滑。PRG4 在关节稳态中发挥着关键作用,并具有软骨保护作用。在创伤后骨关节炎(PTOA)中,正常的 PRG4 生成会受到炎症和不规则机械负荷的影响。SZ软骨细胞(SZC)的表型,包括PRG4的表达,在体外受肌动蛋白细胞骨架的调控。人们对原生关节软骨细胞中肌动蛋白细胞骨架对 PRG4 的调控的了解仍然有限。丝状(F)肌动蛋白细胞骨架是机械刺激和细胞因子激活与深部软骨细胞中PRG4调控之间串联的潜在节点,因此深入了解肌动蛋白对PRG4的调控可能会发现新型PTOA疗法的分子靶点:对PRG4和肌动蛋白组织对SZC表型的调控进行了全面的文献检索:结果:PRG4在体外离体SZC中受到肌动蛋白细胞骨架的强烈调控。结论:基于肌动蛋白的PRG4调控在体外离体SZC中很强:结论:PRG4在原生SZC中基于肌动蛋白的调控尚未完全明了,需要进一步阐明。了解 SZCs 中肌动蛋白对 PRG4 的调控需要体内环境,以进一步挖掘利用肌动蛋白排列治疗关节炎的潜力。
{"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><strong>Objective: </strong>The 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.</p><p><strong>Materials and methods: </strong>A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed.</p><p><strong>Results: </strong>PRG4 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.</p><p><strong>Conclusion: </strong>Actin-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":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MicroRNA-322 Attenuates Cartilage Matrix Degradation in Osteoarthritis via Direct Suppression of TRAF3. MicroRNA-322 通过直接抑制 TRAF3 减缓骨关节炎中软骨基质的降解
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2023-12-14 DOI: 10.1177/19476035231213207
Jirong Wang, Lan Chai, Ying Tang, Guofu Wang, Yizhong Bao, Bo Ma

Objective: Osteoarthritis (OA) is a degenerative joint disease. A growing number of studies have shown that microRNAs (miRNAs) play an important role in the pathogenesis of OA. However, the specific function of miR-322 in OA is unknown. This study was aimed to explore the ability of miR-322 in the cartilage matrix degradation and the mechanism in OA.

Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect miR-322 expression in cartilage and OA-associated gene expression in chondrocytes treated with miR-322 mimics/inhibitors or interleukin (IL)-1β, respectively. The targets of miR-322 were analyzed using software and the luciferase reporter experiment. In vivo, intra-articular injection of miR-322 mimics was administered at the knee of DMM mice. After 12 weeks, the knee joints of mice were collected for histological analysis.

Results: The expression of miR-322 was decreased in knee cartilage of DMM mice and was significantly reduced by IL-1β. miR-322 mimics inhibited IL-1β-induced extracellular matrix degradation, as evidenced by higher expression of Col2α1 and Aggrecan, and lower expression of Adamts5, MMP3, and MMP13. In contrast, miR-322 inhibitor promoted extracellular matrix degradation of chondrocytes. TRAF3 was the predicted target of miR-322 from databases. Luciferase reporter assay verified the targeting relationship between miR-322 and TRAF3. The effect of miR-322 on extracellular matrix degradation was partially reversed by overexpression of TRAF3. In addition, H&E and Safranin-O fast green staining assays in OA mouse models showed that miR-322 mimics attenuated the progression of OA in vivo.

Conclusions: miR-322 suppressed chondrocytes matrix degradation and alleviated OA cartilage injury via inhibition of the TRAF3.

目的:骨关节炎(OA)是一种退行性关节疾病:骨关节炎(OA)是一种退行性关节疾病。越来越多的研究表明,微 RNA(miRNA)在 OA 的发病机制中发挥着重要作用。然而,miR-322 在 OA 中的具体功能尚不清楚。本研究旨在探讨miR-322在软骨基质降解中的能力及其在OA中的作用机制:方法:采用定量反转录聚合酶链反应(qRT-PCR)检测miR-322在软骨中的表达,以及分别用miR-322模拟物/抑制剂或白细胞介素(IL)-1β处理的软骨细胞中OA相关基因的表达。利用软件和荧光素酶报告实验分析了 miR-322 的靶标。在体内,DMM小鼠膝关节内注射miR-322模拟物。12 周后,收集小鼠膝关节进行组织学分析:miR-322模拟物抑制了IL-1β诱导的细胞外基质降解,表现为Col2α1和Aggrecan的表达增加,Adamts5、MMP3和MMP13的表达降低。相反,miR-322 抑制剂则促进软骨细胞的细胞外基质降解。根据数据库预测,TRAF3 是 miR-322 的靶点。荧光素酶报告实验验证了 miR-322 与 TRAF3 的靶向关系。过表达 TRAF3 可部分逆转 miR-322 对细胞外基质降解的影响。结论:miR-322通过抑制TRAF3抑制软骨细胞基质降解,减轻了OA软骨损伤。
{"title":"MicroRNA-322 Attenuates Cartilage Matrix Degradation in Osteoarthritis via Direct Suppression of TRAF3.","authors":"Jirong Wang, Lan Chai, Ying Tang, Guofu Wang, Yizhong Bao, Bo Ma","doi":"10.1177/19476035231213207","DOIUrl":"https://doi.org/10.1177/19476035231213207","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is a degenerative joint disease. A growing number of studies have shown that microRNAs (miRNAs) play an important role in the pathogenesis of OA. However, the specific function of miR-322 in OA is unknown. This study was aimed to explore the ability of miR-322 in the cartilage matrix degradation and the mechanism in OA.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect miR-322 expression in cartilage and OA-associated gene expression in chondrocytes treated with miR-322 mimics/inhibitors or interleukin (IL)-1β, respectively. The targets of miR-322 were analyzed using software and the luciferase reporter experiment. <i>In vivo</i>, intra-articular injection of miR-322 mimics was administered at the knee of DMM mice. After 12 weeks, the knee joints of mice were collected for histological analysis.</p><p><strong>Results: </strong>The expression of miR-322 was decreased in knee cartilage of DMM mice and was significantly reduced by IL-1β. miR-322 mimics inhibited IL-1β-induced extracellular matrix degradation, as evidenced by higher expression of Col2α1 and Aggrecan, and lower expression of Adamts5, MMP3, and MMP13. In contrast, miR-322 inhibitor promoted extracellular matrix degradation of chondrocytes. TRAF3 was the predicted target of miR-322 from databases. Luciferase reporter assay verified the targeting relationship between miR-322 and TRAF3. The effect of miR-322 on extracellular matrix degradation was partially reversed by overexpression of TRAF3. In addition, H&E and Safranin-O fast green staining assays in OA mouse models showed that miR-322 mimics attenuated the progression of OA <i>in vivo</i>.</p><p><strong>Conclusions: </strong>miR-322 suppressed chondrocytes matrix degradation and alleviated OA cartilage injury via inhibition of the TRAF3.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
“Cartilage Injuries of the Foot: What We Do Not Know, We Fear . . .” "足部软骨损伤:我们所不知道的,我们所害怕的......"
IF 2.8 4区 医学 Q1 Health Professions Pub Date : 2023-12-09 DOI: 10.1177/19476035231216088
Jari Dahmen, Masato Takao, Mats Brittberg, Gino M M J Kerkhoffs
{"title":"“Cartilage Injuries of the Foot: What We Do Not Know, We Fear . . .”","authors":"Jari Dahmen, Masato Takao, Mats Brittberg, Gino M M J Kerkhoffs","doi":"10.1177/19476035231216088","DOIUrl":"https://doi.org/10.1177/19476035231216088","url":null,"abstract":"","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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