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Slow acting medications for progressive and painful knee osteoarthritis. How do we assess the benefit to risk of these potentially novel therapies? 治疗进行性和疼痛性膝骨关节炎的慢效药物。我们如何评估这些潜在的新疗法的获益与风险?
Pub Date : 2024-11-27 DOI: 10.1016/j.ocarto.2024.100546
Nancy E. Lane, Lee S. Simon, Jeyanesh Tambiah
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引用次数: 0
MicroRNA-181a/b-1 enhances chondroprogenitor anabolism and downregulates aquaporin-9 MicroRNA-181a/b-1增强软骨祖细胞合成代谢,下调水通道蛋白-9
Pub Date : 2024-11-26 DOI: 10.1016/j.ocarto.2024.100550
Austin Bell-Hensley , Victor Gustavo Balera Brito , Lei Cai , Jin Liu , Kathryn Feeney , Hongjun Zheng , Audrey McAlinden

Objective

Effective osteoarthritis treatments that enhance the anabolic/regenerative capacity of chondrocytes are needed. Studying cartilage development processes may inform us of approaches to control chondrocyte differentiation and anabolism and, ultimately, how to effectively treat OA. MicroRNAs are broad-acting epigenetic regulators known to affect many skeletal processes. Previous reports from our group indicated that miR-181a-1 is upregulated during chondrocyte differentiation. The goal of this study was to determine how the entire miR-181a/b-1 cluster regulates in vitro chondrogenesis.

Design

Precursor miR-181a/b-1 was over-expressed in cartilage progenitor cells using lentiviral technology Transduced cartilage progenitor cells were cultured as micromass pellets in hypoxic conditions and stimulated to undergo chondrogenic differentiation for five weeks. Bulk RNA-sequencing and immunostaining was applied to evaluate chondrogenic differentiation and matrix production.

Results

Immunostaining of cartilage pellet sections showed that miR-181a/b-1 increased mature type II collagen and decreased expression of the chondroprogenitor type IIA collagen isoform. Bulk RNA-Seq at day 7 of chondrogenesis revealed upregulation of pro-anabolic genes such as COL2A1, COL9A2/3, COL11A2 and SNORC. Of the genes significantly downregulated by miR-181a/b-1, aquaporin 9 (AQP9) was the top hit which decreased in expression by over 14-fold. While a predicted target of miR-181a/b, our data showed that this miRNA cluster likely suppresses AQP9 via an indirect targeting mechanism.

Conclusions

Our findings demonstrate a pro-differentiation/anabolic function for miR-181a/b-1 during in vitro chondrogenesis that may be due, in part, to suppression of AQP9. Future studies are needed to elucidate the role of this membrane channel protein in regulating chondrocyte differentiation and homeostasis.
目的研究增强软骨细胞合成代谢/再生能力的有效骨关节炎治疗方法。研究软骨发育过程可以告诉我们控制软骨细胞分化和合成代谢的方法,并最终了解如何有效治疗骨关节炎。microrna是一种广泛作用的表观遗传调节剂,已知可影响许多骨骼过程。我们组之前的报道表明,miR-181a-1在软骨细胞分化过程中上调。本研究的目的是确定整个miR-181a/b-1簇如何调节体外软骨形成。DesignPrecursor miR-181a/b-1通过慢病毒技术在软骨祖细胞中过表达,转导的软骨祖细胞在缺氧条件下作为微团小球培养,并刺激其进行5周的软骨分化。大量rna测序和免疫染色用于评估软骨分化和基质的产生。结果软骨颗粒切片免疫染色显示miR-181a/b-1增加成熟II型胶原,降低软骨祖细胞IIA型胶原异构体的表达。软骨形成第7天的Bulk RNA-Seq显示促合成代谢基因如COL2A1、COL9A2/3、COL11A2和SNORC上调。在miR-181a/b-1显著下调的基因中,水通道蛋白9 (aquaporin 9, AQP9)是最受打击的基因,其表达量下降了14倍以上。虽然miR-181a/b是预测的靶点,但我们的数据显示,该miRNA簇可能通过间接靶向机制抑制AQP9。研究结果表明,miR-181a/b-1在体外软骨形成过程中具有促分化/合成代谢功能,这可能部分归因于AQP9的抑制。未来的研究需要阐明这种膜通道蛋白在调节软骨细胞分化和稳态中的作用。
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引用次数: 0
Safety and preliminary efficacy of transcutaneous auricular vagus nerve stimulation on chronic knee pain: A pilot trial 经皮耳迷走神经刺激治疗慢性膝关节疼痛的安全性和初步疗效:一项先导试验
Pub Date : 2024-11-23 DOI: 10.1016/j.ocarto.2024.100545
Kosaku Aoyagi , Elias Rivas , Roxanna Shababi , Robert Edwards , Michael LaValley , Julia Lechuga , Vitaly Napadow , Tuhina Neogi

Objective

Transcutaneous auricular vagus nerve stimulation (tVNS) may be an innovative treatment for symptoms of knee osteoarthritis (OA) due to possible shared pathological mechanisms between diminished parasympathetic function, central pain mechanisms, and knee pain. Thus, we sought to test the safety and preliminary efficacy of tVNS in people with knee OA.

Design

A pilot trial in which participants received a 60-min tVNS was conducted. At baseline, immediately after, and 15 ​min after tVNS, we assessed knee pain, pressure pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and high-frequency power of heart rate variability (HF). We examined the extent to which these outcome measures changed after tVNS using linear mixed models.

Results

30 participants with knee OA were included, and all completed the intervention without any major side effects. Compared to baseline, knee pain was reduced by 1.27 (95 ​% CI, −1.74, −0.80) immediately after and by 1.87 (−2.33, −1.40) 15 ​min after tVNS; CPM improved by 0.11 (0.04, 0.19) and 0.07 (−0.01, 0.15); and HF improved by 213.29 (−0.38, 426.96) and 234.17 (20.49, 447.84). PPT and TS were not changed after tVNS.

Conclusions

Our preliminary data demonstrated that tVNS may be a safe pain-relieving treatment for people with knee OA. Our findings suggest that improvement of knee pain might be derived from improvement of parasympathetic function and central pain mechanisms as no local therapy was applied. A large study is needed to confirm that tVNS is a novel intervention to ameliorate knee pain in people with knee OA.

Clinical Trial

ClinicalTrials.gov (NCT05625178).
目的:经皮耳迷走神经刺激(tVNS)可能是治疗膝关节骨关节炎(OA)症状的一种创新方法,因为副交感神经功能减退、中枢疼痛机制和膝关节疼痛之间可能存在共同的病理机制。因此,我们试图测试tVNS在膝关节OA患者中的安全性和初步有效性。DesignA进行了一项试点试验,参与者获得了60分钟的电视节目。在基线、tVNS后立即和tVNS后15分钟,我们评估了膝关节疼痛、压痛阈值(PPT)、时间累积(TS)、条理性疼痛调节(CPM)和心率变异性的高频功率(HF)。我们使用线性混合模型检验了tVNS后这些结果测量变化的程度。结果纳入30例膝关节OA患者,所有患者均完成干预,无重大副作用。与基线相比,膝关节疼痛在tVNS后立即减少1.27 (95% CI, - 1.74, - 0.80),在tVNS后15分钟减少1.87 (- 2.33,- 1.40);CPM分别提高0.11(0.04,0.19)和0.07 (- 0.01,0.15);HF分别提高213.29(- 0.38,426.96)和234.17(20.49,447.84)。tVNS后PPT和TS均未改变。结论初步数据表明,tVNS可能是一种安全的缓解膝关节OA患者疼痛的方法。我们的研究结果表明,在没有局部治疗的情况下,膝关节疼痛的改善可能源于副交感神经功能和中枢疼痛机制的改善。需要大量的研究来证实tVNS是一种新的干预措施来改善膝关节OA患者的膝关节疼痛。clinicaltrials .gov (NCT05625178)。
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引用次数: 0
Study protocol for the PICASSO trial: A randomized placebo-controlled trial to investigate the efficacy and safety of intraarticular steroid injections and an occupational therapy intervention in painful inflammatory carpometacarpal-1 osteoarthritis PICASSO 试验研究方案:随机安慰剂对照试验:调查关节内类固醇注射和职业疗法干预对疼痛性炎症性腕掌-1 骨关节炎的疗效和安全性
Pub Date : 2024-11-19 DOI: 10.1016/j.ocarto.2024.100542
Marthe Gløersen , Ingvild Kjeken , A.T. Tveter , Amirhossein Kazemi , Joseph Sexton , Krysia Dziedzic , David T. Felson , Tanja A. Stamm , Ali Guermazi , Merete Hermann-Eriksen , M.I. Sæther , Kristine Lundby , E.L. Esperø , Monika Olsen , K.B. Norheim , Edle Berg Fister , Mari Hoff , Jorunn Kvalø Uleberg , Irina Petrovna Midtgard , Therese Andreassen , Trine Amalie Sjøvold

Objective

Our primary objectives are to assess whether intraarticular corticosteroid injections are superior to saline injections with regards to thumb base pain after 4 weeks, and to compare the efficacy of steroid injections, saline injections, and an occupational therapy intervention on thumb base pain after 12 weeks in people with painful inflammatory osteoarthritis (OA) of the first carpometacarpal (CMC-1) joint.

Design

In this three-armed, double-blind, randomized multicenter trial, 354 participants with painful inflammatory CMC-1 OA from six Norwegian hospitals are recruited. Participants are randomized 1:1:1 to intraarticular steroid or saline injections in the CMC-1 joint or a multimodal occupational therapy intervention. The primary outcomes are thumb base pain measured on a numeric rating scale (NRS, range: 0–10) after 4 weeks and 12 weeks. Key secondary outcomes include synovitis by Magnetic Resonance Imaging (MRI) after 4 weeks and hand function by the Measure of Activity Performance of the Hand (MAP-Hand) questionnaire after 12 and 24 weeks. Other secondary outcomes are synovitis by clinical examination and ultrasound, measures of pain, function, stiffness, and health-related quality of life, and direct and indirect costs. Adverse events are recorded at each visit. The duration of the randomized controlled trial is 24 weeks, followed by an 80-week open-label observational phase to investigate the long-term efficacy and safety of repeated steroid injections and the occupational therapy intervention.

Conclusions

The results from this trial will have important clinical implications and influence future guidelines on OA management of the CMC-1 joint.

Clinical trial registration

EU-CT 2023-505254-17-00, NCT06084364.
目标我们的主要目标是评估关节内皮质类固醇注射在4周后拇指根部疼痛方面是否优于生理盐水注射,并比较类固醇注射、生理盐水注射和职业疗法干预对第一腕掌关节(CMC-1)疼痛性炎症性骨关节炎(OA)患者12周后拇指根部疼痛的疗效。设计在这项三臂、双盲、随机多中心试验中,从挪威六家医院招募了354名患有第一腕掌关节疼痛性炎症性骨关节炎的患者。参与者按1:1:1的比例随机接受CMC-1关节内类固醇或生理盐水注射或多模式职业疗法干预。主要结果为 4 周和 12 周后以数字评分量表(NRS,范围:0-10)测量的拇指根部疼痛。主要次要结果包括:4 周后通过磁共振成像(MRI)检查滑膜炎;12 周和 24 周后通过手部活动能力测量(MAP-Hand)问卷调查手部功能。其他次要结果包括临床检查和超声波检查发现的滑膜炎,疼痛、功能、僵硬度和健康相关生活质量的测量,以及直接和间接成本。每次就诊都会记录不良事件。随机对照试验的持续时间为 24 周,随后是为期 80 周的开放标签观察阶段,以调查重复类固醇注射和职业疗法干预的长期疗效和安全性。临床试验注册EU-CT 2023-505254-17-00,NCT06084364。
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引用次数: 0
Proteomic analysis reveals biomarkers associated with performance-based joint function and patient-reported outcomes in knee osteoarthritis 蛋白质组分析揭示了与膝关节骨性关节炎基于表现的关节功能和患者报告结果相关的生物标志物
Pub Date : 2024-11-16 DOI: 10.1016/j.ocarto.2024.100543
Josefine E. Naili , Aisha S. Ahmed , Margareta Hedström , Morten Bilde Simonsen , Eva W. Broström , Helena Erlandsson Harris , Ákos Végvári , Cecilia Aulin

Objective

This study aimed to identify proteins associated with clinical manifestations of knee osteoarthritis (KOA), including performance-based joint function and patient-reported outcome measures (PROM).

Methods

This cross-sectional exploratory study included thirteen individuals with KOA and eleven age-matched controls. All participants performed the 30s Single Leg Mini Squat test and 30s Sit-to-Stand test with simultaneous recording of joint kinematics. Individuals with KOA completed the Knee Injury and Osteoarthritis Outcome Score and Forgotten Joint Score-12. Proteins were determined by quantitative mass spectrometry (MS) in plasma. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and Reactome enrichment analysis of the proteome were conducted to identify activated pathways and groups.

Results

Performance-based function was worse in individuals with KOA compared to controls, and they reported higher levels of pain. MS analysis identified 82 differentially expressed proteins (DEPs) in KOA (28 upregulated, 54 downregulated of 321 detected proteins). PCA displayed distinct features between KOA and controls, similar to HCA, which distinguished two major clusters. Enrichment analysis displayed platelet activation and degranulation, neutrophil, and extracellular matrix (ECM)-related pathways. From the proteome, 23 DEPs were associated with different aspects of joint function, and 25 DEPs with PROM.

Conclusions

Individuals with KOA differed from controls across all three assessment modalities; they presented worse joint function, higher levels of pain, and an altered plasma protein profile. Multiple associations were observed between up- and downregulated DEPs and clinical manifestations. The described study protocol shows promise for performing multivariate analyses for future subgrouping of individuals with KOA.
目的本研究旨在确定与膝关节骨性关节炎(KOA)临床表现相关的蛋白质,包括基于表现的关节功能和患者报告的结果测量(PROM)。方法本横断面探索性研究包括 13 名 KOA 患者和 11 名年龄匹配的对照组。所有参与者都进行了 30 秒钟单腿迷你深蹲测试和 30 秒钟坐立测试,并同时记录了关节运动学数据。KOA患者完成了膝关节损伤和骨关节炎结果评分以及被遗忘的关节评分-12。血浆中的蛋白质通过定量质谱法(MS)进行测定。对蛋白质组进行了主成分分析(PCA)、层次聚类分析(HCA)和反应组富集分析,以确定激活的通路和组别。质谱分析在 KOA 患者中发现了 82 个差异表达蛋白 (DEPs)(在 321 个检测到的蛋白中,28 个上调,54 个下调)。PCA 显示了 KOA 和对照组之间的不同特征,这与 HCA 相似,后者区分了两个主要群组。富集分析显示了血小板活化和脱颗粒、中性粒细胞和细胞外基质(ECM)相关途径。在蛋白质组中,23 个 DEPs 与关节功能的不同方面相关,25 个 DEPs 与 PROM 相关。在上调和下调的 DEPs 与临床表现之间存在多种关联。所描述的研究方案表明,在未来对KOA患者进行分组时,有望进行多变量分析。
{"title":"Proteomic analysis reveals biomarkers associated with performance-based joint function and patient-reported outcomes in knee osteoarthritis","authors":"Josefine E. Naili ,&nbsp;Aisha S. Ahmed ,&nbsp;Margareta Hedström ,&nbsp;Morten Bilde Simonsen ,&nbsp;Eva W. Broström ,&nbsp;Helena Erlandsson Harris ,&nbsp;Ákos Végvári ,&nbsp;Cecilia Aulin","doi":"10.1016/j.ocarto.2024.100543","DOIUrl":"10.1016/j.ocarto.2024.100543","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to identify proteins associated with clinical manifestations of knee osteoarthritis (KOA), including performance-based joint function and patient-reported outcome measures (PROM).</div></div><div><h3>Methods</h3><div>This cross-sectional exploratory study included thirteen individuals with KOA and eleven age-matched controls. All participants performed the 30s Single Leg Mini Squat test and 30s Sit-to-Stand test with simultaneous recording of joint kinematics. Individuals with KOA completed the Knee Injury and Osteoarthritis Outcome Score and Forgotten Joint Score-12. Proteins were determined by quantitative mass spectrometry (MS) in plasma. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and Reactome enrichment analysis of the proteome were conducted to identify activated pathways and groups.</div></div><div><h3>Results</h3><div>Performance-based function was worse in individuals with KOA compared to controls, and they reported higher levels of pain. MS analysis identified 82 differentially expressed proteins (DEPs) in KOA (28 upregulated, 54 downregulated of 321 detected proteins). PCA displayed distinct features between KOA and controls, similar to HCA, which distinguished two major clusters. Enrichment analysis displayed platelet activation and degranulation, neutrophil, and extracellular matrix (ECM)-related pathways. From the proteome, 23 DEPs were associated with different aspects of joint function, and 25 DEPs with PROM.</div></div><div><h3>Conclusions</h3><div>Individuals with KOA differed from controls across all three assessment modalities; they presented worse joint function, higher levels of pain, and an altered plasma protein profile. Multiple associations were observed between up- and downregulated DEPs and clinical manifestations. The described study protocol shows promise for performing multivariate analyses for future subgrouping of individuals with KOA.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"7 1","pages":"Article 100543"},"PeriodicalIF":0.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A scoping review of statistical methods to investigate colocalization between genetic associations and microRNA expression in osteoarthritis 研究骨关节炎中遗传关联与 microRNA 表达之间共定位的统计方法范围综述
Pub Date : 2024-11-08 DOI: 10.1016/j.ocarto.2024.100540
Kathleen Zang , Myriam Brossard , Thomas Wilson , Shabana Amanda Ali , Osvaldo Espin-Garcia

Background

Genetic colocalization analysis is a statistical method that evaluates whether two traits (e.g., osteoarthritis [OA] risk and microRNA [miRNA] expression levels) share the same or distinct genetic association signals in a locus typically identified in genome-wide association studies (GWAS). This method is useful for providing insights into the biological relevance of genetic association signals, particularly in intergenic regions, which can help to elucidate disease mechanisms in OA and other complex traits.

Objectives

To review the existing literature on genetic colocalization methods, assess their suitability for studying OA, and investigate their capacity to integrate miRNA data, while bearing in view their statistical assumptions.

Design

We followed scoping review methodology and used Covidence software for data management. Search terms for colocalization, GWAS, and genetic or statistical models were used in the databases MEDLINE and EMBASE, searched till March 4, 2024.

Results

Our search returned 546 peer-reviewed papers, of which 96 were included following title/abstract and full-text screening. Based on both cumulative and annual publication counts, the most cited method for colocalization analysis was coloc. Four papers examined OA-related phenotypes, and none examined miRNA. An approach to colocalization analysis using miRNA was postulated based on further hand-searching.

Conclusions

Colocalization analysis is a largely unexplored method in OA. Many of the approaches to colocalization analysis identified in this review, including the integration of GWAS and miRNA data, may help to elucidate genetic and epigenetic factors implicated in OA and other complex traits.
背景遗传共定位分析是一种统计方法,用于评估两个性状(如骨关节炎[OA]风险和microRNA[miRNA]表达水平)在全基因组关联研究(GWAS)中通常确定的位点上是否具有相同或不同的遗传关联信号。这种方法有助于深入了解遗传关联信号的生物学相关性,尤其是基因间区域的相关性,从而有助于阐明 OA 和其他复杂性状的疾病机理。目的综述有关遗传共定位方法的现有文献,评估这些方法对研究 OA 的适用性,并研究它们整合 miRNA 数据的能力,同时考虑到它们的统计假设。在 MEDLINE 和 EMBASE 数据库中使用了共定位、GWAS 和遗传或统计模型等检索词,检索期至 2024 年 3 月 4 日。结果我们检索到了 546 篇经同行评审的论文,其中 96 篇经过标题/摘要和全文筛选后被收录。根据累计和年度发表论文数,被引用最多的共聚焦分析方法是coloc。四篇论文研究了 OA 相关表型,没有一篇研究 miRNA。在进一步手工搜索的基础上,推测出了一种利用 miRNA 进行共定位分析的方法。本综述中确定的许多共定位分析方法,包括整合 GWAS 和 miRNA 数据,可能有助于阐明与 OA 和其他复杂性状有关的遗传和表观遗传因素。
{"title":"A scoping review of statistical methods to investigate colocalization between genetic associations and microRNA expression in osteoarthritis","authors":"Kathleen Zang ,&nbsp;Myriam Brossard ,&nbsp;Thomas Wilson ,&nbsp;Shabana Amanda Ali ,&nbsp;Osvaldo Espin-Garcia","doi":"10.1016/j.ocarto.2024.100540","DOIUrl":"10.1016/j.ocarto.2024.100540","url":null,"abstract":"<div><h3>Background</h3><div>Genetic colocalization analysis is a statistical method that evaluates whether two traits (e.g., osteoarthritis [OA] risk and microRNA [miRNA] expression levels) share the same or distinct genetic association signals in a locus typically identified in genome-wide association studies (GWAS). This method is useful for providing insights into the biological relevance of genetic association signals, particularly in intergenic regions, which can help to elucidate disease mechanisms in OA and other complex traits.</div></div><div><h3>Objectives</h3><div>To review the existing literature on genetic colocalization methods, assess their suitability for studying OA, and investigate their capacity to integrate miRNA data, while bearing in view their statistical assumptions.</div></div><div><h3>Design</h3><div>We followed scoping review methodology and used Covidence software for data management. Search terms for colocalization, GWAS, and genetic or statistical models were used in the databases MEDLINE and EMBASE, searched till March 4, 2024.</div></div><div><h3>Results</h3><div>Our search returned 546 peer-reviewed papers, of which 96 were included following title/abstract and full-text screening. Based on both cumulative and annual publication counts, the most cited method for colocalization analysis was coloc. Four papers examined OA-related phenotypes, and none examined miRNA. An approach to colocalization analysis using miRNA was postulated based on further hand-searching.</div></div><div><h3>Conclusions</h3><div>Colocalization analysis is a largely unexplored method in OA. Many of the approaches to colocalization analysis identified in this review, including the integration of GWAS and miRNA data, may help to elucidate genetic and epigenetic factors implicated in OA and other complex traits.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100540"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of all-cause mortality in patients with knee osteoarthritis: A systematic review and meta-analysis of cohort studies 膝关节骨性关节炎患者的全因死亡风险:队列研究的系统回顾和荟萃分析
Pub Date : 2024-11-08 DOI: 10.1016/j.ocarto.2024.100541
Pei-En Kao , Amy Ker

Objective

This systematic review and meta-analysis aimed to evaluate the risk of all-cause mortality in patients with knee osteoarthritis (OA).

Design

Comprehensive searches were conducted in PubMed, Embase, and the Cochrane Library on September 01, 2024. The review included cohort studies reporting risk estimates of all-cause mortality in knee OA patients compared to those without knee OA. Using a random-effects model, the pooled hazard ratios (HRs) were calculated. Subgroup analyses were performed according to the classification of knee OA, including radiographic knee OA only, symptomatic knee OA only, and radiographic and symptomatic knee OA.

Results

A total of 15 cohort studies involving 1,023,799 participants were included in the systematic review, with 14 studies remaining for the meta-analysis. The meta-analysis revealed that knee OA patients had an increased risk of all-cause mortality compared to those without knee OA (pooled HR: 1.21; 95% confidence interval [CI]: 1.02, 1.45). Subgroup analyses indicated the mixed results, including radiographic knee OA only (pooled HR: 1.11; 95% CI: 0.97, 1.26), symptomatic knee OA only (pooled HR: 1.07; 95% CI: 0.80, 1.43), and radiographic and symptomatic knee OA (pooled HR: 1.58; 95% CI: 1.20, 2.07).

Conclusions

This meta-analysis supports an association between knee OA and an increased risk of all-cause mortality, with a particularly pronounced risk observed in radiographic and symptomatic knee OA patients. Further research is needed to determine if OA at other sites also correlates with a higher risk of all-cause mortality.
设计于 2024 年 9 月 1 日在 PubMed、Embase 和 Cochrane 图书馆进行了全面检索。综述纳入了报告膝关节OA患者与无膝关节OA患者全因死亡率风险估计值的队列研究。采用随机效应模型计算了汇总的危险比(HRs)。根据膝关节OA的分类进行了分组分析,包括仅有放射学检查结果的膝关节OA、仅有症状的膝关节OA以及有放射学检查结果和症状的膝关节OA。结果 系统综述共纳入了15项队列研究,涉及1,023,799名参与者,剩下的14项研究用于荟萃分析。荟萃分析显示,与无膝关节OA的患者相比,膝关节OA患者的全因死亡风险增加(汇总HR:1.21;95%置信区间[CI]:1.02,1.45)。亚组分析表明结果不一,包括仅有放射性膝关节OA(汇总HR:1.11;95% CI:0.97,1.26)、仅有症状膝关节OA(汇总HR:1.07;95% CI:0.80,1.43)以及有放射性和症状膝关节OA(汇总HR:1.结论这项荟萃分析支持膝关节 OA 与全因死亡风险增加之间存在关联,在影像学和无症状膝关节 OA 患者中观察到的风险尤其明显。要确定其他部位的 OA 是否也与全因死亡风险升高有关,还需要进一步的研究。
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引用次数: 0
Peripheral arterial pathology and osteoarthritis of the knee: US examination of arterial wall stiffness, thickness, and flow characteristics 外周动脉病理学与膝关节骨性关节炎:动脉壁硬度、厚度和血流特征的 US 检查
Pub Date : 2024-10-29 DOI: 10.1016/j.ocarto.2024.100537
Jon Olansen , Minglang Yin , Janine Molino , Thomas Carruthers , Derek Jenkins , George Karniadakis , Roy K. Aaron

Background

Osteoarthritis (OA) is a widespread chronic joint disorder characterized by the degeneration of articular cartilage, extensive bone remodeling, ligamentous fibrosis, and synovial inflammation impacting millions. Shared factors like phenotypic similarities, hypofibrinolysis, and inflammation constitute similarities in pathophysiology and clinical manifestations between OA and peripheral vascular disease (PVD). This study investigated peripheral arterial flow characteristics, vascular wall thickness, and stiffness in knee OA to clarify a potential association with early atherosclerosis.

Methods

The OA cohort consisted of 35 knees with a mean age of 69 years. The control cohort consisted of 58 knees with a mean age of 68 years. Subjects underwent arterial ultrasound scanning of the common femoral, superficial femoral, and popliteal arteries. Data measured included peak systolic volumetric flow, intima-media thickness, systolic and diastolic vessel diameter, and simultaneous EKG and flow curves. Structural and functional vascular data were quantified using the incremental Young's modulus, pulse wave velocity (PWV), and distensibility.

Results

Significantly elevated arterial volumetric flow, measures of arterial stiffness, and intima-media wall thickness were observed in those with OA compared to those without. PWV as calculated by the Bramwell-Hill equation were found to be significantly greater in all three vessels of patients with OA.

Conclusions

This study supports the association between peripheral arterial pathology and knee OA, consistent with shared clinical and phenotypic traits. The observed characteristics of early vascular pathology suggest potential pathophysiologic linkages between OA and PVD. This foundational framework provides avenues for mechanistic studies exploring the relationship between these two disease processes.
背景骨关节炎(OA)是一种广泛存在的慢性关节疾病,其特点是关节软骨退化、广泛的骨重塑、韧带纤维化和滑膜炎症,影响数百万人。表型相似、纤溶不足和炎症等共同因素构成了 OA 和外周血管疾病(PVD)在病理生理学和临床表现上的相似性。本研究调查了膝关节 OA 的外周动脉血流特征、血管壁厚度和僵硬度,以明确其与早期动脉粥样硬化的潜在联系。对照组包括58个膝关节,平均年龄68岁。受试者接受了股总动脉、股浅动脉和腘动脉的动脉超声扫描。测量数据包括收缩期峰值容积流量、内膜厚度、收缩期和舒张期血管直径以及同步心电图和血流曲线。使用增量杨氏模量、脉搏波速度(PWV)和扩张性对结构性和功能性血管数据进行量化。根据布拉姆韦尔-希尔方程计算得出的脉搏波速度在 OA 患者的所有三条血管中都明显增大。观察到的早期血管病理学特征表明,OA 和 PVD 之间存在潜在的病理生理学联系。这一基础框架为探索这两种疾病过程之间关系的机理研究提供了途径。
{"title":"Peripheral arterial pathology and osteoarthritis of the knee: US examination of arterial wall stiffness, thickness, and flow characteristics","authors":"Jon Olansen ,&nbsp;Minglang Yin ,&nbsp;Janine Molino ,&nbsp;Thomas Carruthers ,&nbsp;Derek Jenkins ,&nbsp;George Karniadakis ,&nbsp;Roy K. Aaron","doi":"10.1016/j.ocarto.2024.100537","DOIUrl":"10.1016/j.ocarto.2024.100537","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a widespread chronic joint disorder characterized by the degeneration of articular cartilage, extensive bone remodeling, ligamentous fibrosis, and synovial inflammation impacting millions. Shared factors like phenotypic similarities, hypofibrinolysis, and inflammation constitute similarities in pathophysiology and clinical manifestations between OA and peripheral vascular disease (PVD). This study investigated peripheral arterial flow characteristics, vascular wall thickness, and stiffness in knee OA to clarify a potential association with early atherosclerosis.</div></div><div><h3>Methods</h3><div>The OA cohort consisted of 35 knees with a mean age of 69 years. The control cohort consisted of 58 knees with a mean age of 68 years. Subjects underwent arterial ultrasound scanning of the common femoral, superficial femoral, and popliteal arteries. Data measured included peak systolic volumetric flow, intima-media thickness, systolic and diastolic vessel diameter, and simultaneous EKG and flow curves. Structural and functional vascular data were quantified using the incremental Young's modulus, pulse wave velocity (PWV), and distensibility.</div></div><div><h3>Results</h3><div>Significantly elevated arterial volumetric flow, measures of arterial stiffness, and intima-media wall thickness were observed in those with OA compared to those without. PWV as calculated by the Bramwell-Hill equation were found to be significantly greater in all three vessels of patients with OA.</div></div><div><h3>Conclusions</h3><div>This study supports the association between peripheral arterial pathology and knee OA, consistent with shared clinical and phenotypic traits. The observed characteristics of early vascular pathology suggest potential pathophysiologic linkages between OA and PVD. This foundational framework provides avenues for mechanistic studies exploring the relationship between these two disease processes.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100537"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of cartilage T1ρ and T2 relaxation time measurement with hip osteoarthritis progression: A 5-year longitudinal study using voxel-based relaxometry and Z-score normalization 软骨 T1ρ 和 T2 松弛时间测量与髋关节骨关节炎进展的关系:使用基于体素的弛豫测量法和Z-score归一化进行的一项为期5年的纵向研究
Pub Date : 2024-10-28 DOI: 10.1016/j.ocarto.2024.100538
Rafeek Thahakoya , Koren E. Roach , Misung Han , Rupsa Bhattacharjee , Fei Jiang , Johanna Luitjens , Emma Bahroos , Valentina Pedoia , Richard B. Souza , Sharmila Majumdar
<div><h3>Objective</h3><div>To study the longitudinal changes of cartilage <span><math><mrow><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi><mspace></mspace></mrow></msub></mrow></math></span> and <span><math><mrow><msub><mi>T</mi><mn>2</mn></msub></mrow></math></span> relaxation time measurements in hip-OA patients.</div></div><div><h3>Methods</h3><div>A calibration study compared two scanner data, Scanner-1 (GE Discovery MR750 3.0T) with unilateral acquisition protocol and Scanner-2 (GE Signa Premier 3.0T) with bilateral acquisition protocol, using nine subjects(average age ​= ​40.33 ​± ​13.53 years, 5 females), including one hip-OA subject. Quantified parameters from the Scanner-2 were adjusted using voxel-based relaxometry(VBR) and Z-score normalization to reduce the inter-scanner variability. Eighteen hip-OA Subjects (age ​= ​53.11 ​± ​14.96 years, 12 females) were recruited to the longitudinal variability study from 2016, comprising five assessments at 1-year intervals. Baseline to 3rd-year data used unilateral acquisition with Scanner-1, while 4th-year data used bilateral acquisition with Scanner-2. A linear mixed-effects model(LME) assessed trajectory analyses, with acquisition year, age, sex, body mass index(BMI), and Kellgren-Lawrence(KL) score as predictor variables and cartilage mean <span><math><mrow><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi><mspace></mspace></mrow></msub></mrow></math></span> and <span><math><mrow><msub><mi>T</mi><mn>2</mn></msub></mrow></math></span> values as outcomes.</div></div><div><h3>Results</h3><div>VBR analysis after Z-score normalization showed that only a few of the whole cartilage voxels had significant differences in <span><math><mrow><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi><mspace></mspace></mrow></msub><mo>(</mo></mrow></math></span>femur-2.36 ​% and acetabular-3.23 ​%) and <span><math><mrow><msub><mi>T</mi><mn>2</mn></msub></mrow></math></span> (femur-2.30 ​% and acetabular-2.94 ​%) values between the scanners. The LME analysis showed that the BMI predictor variable was significantly correlated with the femur <span><math><mrow><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi><mspace></mspace></mrow></msub></mrow></math></span> (p ​< ​0.0001) and <span><math><mrow><msub><mi>T</mi><mn>2</mn></msub></mrow></math></span> (p ​< ​0.0001) and acetabular <span><math><mrow><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi><mspace></mspace></mrow></msub></mrow></math></span> (p ​< ​0.0001) and <span><math><mrow><msub><mi>T</mi><mn>2</mn></msub></mrow></math></span> (p ​< ​0.0001) cartilage region.</div></div><div><h3>Conclusion</h3><div>The calibration study demonstrated the effectiveness of VBR and Z-score normalization in reducing inter-scanner variability. The longitudinal study revealed a significant correlation between <span><math><mrow><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi><mspace></mspace></mrow></msub></mrow></math></span> and <span><math><mrow><msub><mi>T</mi><mn>2</mn></msub></mrow></math></span> value
方法校准研究比较了两台扫描仪的数据,即采用单侧采集方案的扫描仪-1(GE Discovery MR750 3.0T)和采用双侧采集方案的扫描仪-2(GE Signa Premier 3.0T)。使用基于体素的弛豫测量法(VBR)和Z-score归一化法调整扫描仪-2的量化参数,以减少扫描仪之间的差异。自2016年起,18名髋关节OA受试者(年龄=53.11 ± 14.96岁,12名女性)被纳入纵向变异性研究,包括5次评估,每次间隔1年。基线至第三年的数据使用扫描仪-1进行单侧采集,第四年的数据使用扫描仪-2进行双侧采集。线性混合效应模型(LME)评估了轨迹分析,采集年份、年龄、性别、体重指数(BMI)和Kellgren-Lawrence(KL)评分为预测变量,软骨平均T1ρ和T2值为结果。结果 Z-score归一化后的VBR分析表明,只有少数整体软骨体素的T1ρ(股骨-2.36%,髋臼-3.23%)和T2(股骨-2.30%,髋臼-2.94%)值在扫描仪之间存在显著差异。LME 分析表明,BMI 预测变量与股骨 T1ρ (p < 0.0001) 和 T2 (p < 0.0001) 以及髋臼 T1ρ (p < 0.0001) 和 T2 (p < 0.0001) 软骨区域显著相关。纵向研究显示,软骨的 T1ρ 和 T2 值与体重指数之间存在显著的相关性;随着时间的推移,某些软骨亚区的 T1ρ 和 T2 值也会增加。
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Souza ,&nbsp;Sharmila Majumdar","doi":"10.1016/j.ocarto.2024.100538","DOIUrl":"10.1016/j.ocarto.2024.100538","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To study the longitudinal changes of cartilage &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; relaxation time measurements in hip-OA patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A calibration study compared two scanner data, Scanner-1 (GE Discovery MR750 3.0T) with unilateral acquisition protocol and Scanner-2 (GE Signa Premier 3.0T) with bilateral acquisition protocol, using nine subjects(average age ​= ​40.33 ​± ​13.53 years, 5 females), including one hip-OA subject. Quantified parameters from the Scanner-2 were adjusted using voxel-based relaxometry(VBR) and Z-score normalization to reduce the inter-scanner variability. Eighteen hip-OA Subjects (age ​= ​53.11 ​± ​14.96 years, 12 females) were recruited to the longitudinal variability study from 2016, comprising five assessments at 1-year intervals. Baseline to 3rd-year data used unilateral acquisition with Scanner-1, while 4th-year data used bilateral acquisition with Scanner-2. A linear mixed-effects model(LME) assessed trajectory analyses, with acquisition year, age, sex, body mass index(BMI), and Kellgren-Lawrence(KL) score as predictor variables and cartilage mean &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; values as outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;VBR analysis after Z-score normalization showed that only a few of the whole cartilage voxels had significant differences in &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;(&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;femur-2.36 ​% and acetabular-3.23 ​%) and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; (femur-2.30 ​% and acetabular-2.94 ​%) values between the scanners. The LME analysis showed that the BMI predictor variable was significantly correlated with the femur &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; (p ​&lt; ​0.0001) and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; (p ​&lt; ​0.0001) and acetabular &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; (p ​&lt; ​0.0001) and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; (p ​&lt; ​0.0001) cartilage region.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The calibration study demonstrated the effectiveness of VBR and Z-score normalization in reducing inter-scanner variability. The longitudinal study revealed a significant correlation between &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;mi&gt;ρ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; value","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 4","pages":"Article 100538"},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bone marrow lesions in osteoarthritis: Characterising genetic and histological changes to understand disease pathophysiology 骨关节炎的骨髓病变:描述遗传和组织学变化,了解疾病病理生理学
Pub Date : 2024-10-26 DOI: 10.1016/j.ocarto.2024.100531
Nidhi Sofat , Franklyn Arron Howe
Osteoarthritis (OA) is a chronic debilitating condition that affects the whole joint. There are several sources of pain in OA that include the synovium, bone, including osteophytes and more recently bone marrow lesions (BML) that correlate with pain. Recent studies have shown that the bone compartment contributes to pain in OA through the development of OA-BMLs which are richly innervated and demonstrate angiogenesis. The synovium is also innervated in OA tissue and is another distinct source of pain, with imaging and genetic studies supporting the observation that synovitis is an important component of pain in OA. Previous studies using magnetic resonance imaging (MRI) have shown that bone marrow lesions (BMLs), observed as high intensity signal on T2 fat-suppressed imaging sequences, are commonly found in OA and are associated with progression of pain symptoms. Recent studies have described the genetic signature of BMLs and the characteristic histological changes of BML tissue. In this narrative review we describe the recent developments in the discovery of the gene expression profiles identified from BMLs. We also review the recently characterised histological changes from BMLs in large weight-bearing joints including the knee and hip. Finally, we discuss the implications of new genetic and histological findings in BML in the context of new developments for pharmacological therapies in OA.
骨关节炎(OA)是一种影响整个关节的慢性衰弱性疾病。骨关节炎的疼痛有多种来源,包括滑膜、骨骼(包括骨质增生)以及最近出现的与疼痛相关的骨髓病变(BML)。最近的研究表明,骨区通过发育 OA-BML(具有丰富神经支配和血管生成功能)而导致 OA 疼痛。滑膜在 OA 组织中也有神经支配,是另一个独特的疼痛源,影像学和遗传学研究支持滑膜炎是 OA 疼痛重要组成部分的观点。以往利用磁共振成像(MRI)进行的研究表明,骨髓病变(BMLs)在 T2 脂肪抑制成像序列上表现为高强度信号,常见于 OA 中,并与疼痛症状的进展有关。最近的研究描述了 BMLs 的遗传特征和 BML 组织的特征性组织学变化。在这篇叙述性综述中,我们介绍了发现 BMLs 基因表达谱的最新进展。我们还回顾了最近在膝关节和髋关节等大型负重关节中发现的 BML 组织学变化特征。最后,我们结合 OA 药物疗法的新进展,讨论了 BML 基因和组织学新发现的意义。
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引用次数: 0
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Osteoarthritis and cartilage open
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