Osteoarthritis and Cartilage最新文献_第9页

Frequent use of prescription NSAIDs among people with knee or hip osteoarthritis despite contraindications to or precautions with NSAIDs 尽管有非甾体抗炎药禁忌症或注意事项，膝关节或髋关节骨性关节炎患者仍频繁使用处方非甾体抗炎药。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-26 DOI: 10.1016/j.joca.2024.07.010

Tuhina Neogi , Andrea Dell’Isola , Martin Englund , Aleksandra Turkiewicz

Objective

To describe the use of non-steroidal anti-inflammatory drugs (NSAID), opioids, and physiotherapy (PT) among persons with newly diagnosed knee or hip osteoarthritis (OA) with and without NSAID contraindications or precautions.

Design

We used population-based register data to identify adults aged ≥35 as of January 1, 2014, residing in Skåne region (Sweden) between 2004 and 2013, without a previous knee or hip OA diagnosis. Among this cohort, we identified people with incident knee or hip OA diagnosis between 2014 and 2018 and the presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. We estimated the risk of 1) regular oral NSAID use, 2) regular opioid use, and 3) PT during the first year after diagnosis among those with vs. without contraindications or precautions using confounder-adjusted logistic regression with standardization.

Results

We identified 35,173 persons with newly diagnosed OA, of whom 3257 and 8351 had ≥1 contraindication to oral NSAIDs and ≥1 precaution, respectively. Overall, 27% of individuals used oral NSAIDs (with or without opioids or PT), 10% used opioids, and 57% attended PT. Among patients with contraindications, 21% used oral NSAIDs compared to 31% without (absolute adjusted difference −0.06 (95% CIs: −0.08, −0.05)), 53% vs 59% used PT (adjusted difference −0.03 (−0.05, −0.01)), while 14% vs. 8% had prescribed dispensed opioids (adjusted difference 0.02 (0.01, 0.03)). Similar results were observed for those with precautions.

Conclusions

We highlight the need for safer treatment options. People with OA and contraindications/precautions to NSAIDs have a higher risk of opioid use, slightly lower risk of PT use, and continue to be prescribed NSAIDs.

目的描述新诊断为膝关节或髋关节骨性关节炎（OA）的患者使用非甾体类抗炎药（NSAID）、阿片类药物和物理治疗（PT）的情况，包括有无NSAID禁忌症或注意事项：我们利用基于人口的登记数据，对 2004-2013 年间居住在斯科纳地区（瑞典）、截至 2014 年 1 月 1 日年龄≥35 岁、既往未确诊过膝关节或髋关节 OA 的成年人进行了识别。在这一队列中，我们确定了在 2014-2018 年间诊断出膝关节或髋关节 OA 的人群，以及在诊断出 OA 时是否存在口服非甾体抗炎药的禁忌症或预防措施的人群。我们估计了以下情况的风险使用混杂因素调整的标准化逻辑回归，我们估算了：1）定期使用口服非甾体抗炎药；2）定期使用阿片类药物；3）在诊断后第一年内，有禁忌症或预防措施与无禁忌症或预防措施者的 PT 风险：我们发现了35173名新确诊的OA患者，其中3257人和8351人分别有≥1个口服非甾体抗炎药禁忌症和≥1个预防措施。总体而言，27%的人使用了口服非甾体抗炎药（使用或不使用阿片类药物或PT），10%的人使用了阿片类药物，57%的人参加了PT。在有禁忌症的患者中，21%的人使用口服非甾体抗炎药，而 31% 的人不使用（调整后绝对差异为 -0.06 (95% CIs: -0.08, -0.05)）；53% 的人使用 PT，而 59% 的人不使用 PT（调整后差异为 -0.03 (-0.05, -0.01)）；14% 的人使用处方配发的阿片类药物，而 8% 的人不使用处方配发的阿片类药物（调整后差异为 0.02 (0.01, 0.03)）。在有预防措施的人群中也观察到了类似的结果：我们强调需要更安全的治疗方案。患有 OA 且有非甾体抗炎药禁忌症/注意事项的患者使用阿片类药物的风险较高，使用 PT 的风险略低，且继续被开具非甾体抗炎药处方：研究中使用的所有数据均可向瑞典国家有关部门索取。

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引用次数: 0

Epigenomic differences between osteoarthritis grades in primary cartilage 原发性软骨中不同等级骨关节炎的表观基因组差异

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-23 DOI: 10.1016/j.joca.2024.07.008

Peter Kreitmaier , Diane Swift , J. Mark Wilkinson , Eleftheria Zeggini

Objective

Osteoarthritis is a common and complex joint disorder that shows higher prevalence and greater disease severity in women. Here, we investigate genome-wide methylation profiles of primary chondrocytes from osteoarthritis patients.

Design

We compare genome-wide methylation profiles of macroscopically intact (low-grade) and degraded (high-grade) osteoarthritis cartilage samples matched from osteoarthritis patients undergoing knee replacement surgery. We perform an epigenome-wide association study for cartilage degeneration across 170 patients and separately in 96 women and 74 men.

Results

We reveal widespread epigenetic differences with enrichments of nervous system and apoptosis-related processes. We further identify substantial similarities between sexes, but also sex-specific markers and pathways.

Conclusions

Together, we provide the largest genome-wide methylation profiles of primary cartilage to date with enhanced and sex-specific insights into epigenetic processes underlying osteoarthritis progression.

目的：骨关节炎是一种常见且复杂的关节疾病，女性发病率更高，病情也更严重。在此，我们研究了骨关节炎患者原发性软骨细胞的全基因组甲基化图谱：我们比较了与接受膝关节置换手术的骨关节炎患者相匹配的宏观完整（低级）和退化（高级）骨关节炎软骨样本的全基因组甲基化图谱。我们对170名患者中的96名女性和74名男性分别进行了软骨退化表观基因组关联研究（EWAS）：结果：我们发现了广泛的表观遗传学差异，其中神经系统和细胞凋亡相关过程的差异较大。结果：我们发现了广泛的表观遗传学差异，其中神经系统和细胞凋亡相关过程富集，我们还发现了两性之间的大量相似性，以及性别特异性标记和通路：总之，我们提供了迄今为止最大规模的原发性软骨全基因组甲基化图谱，增强了对骨关节炎进展的表观遗传过程的洞察力，并具有性别特异性。

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引用次数: 0

People with short symptom duration of knee osteoarthritis benefit more from exercise therapy than people with longer symptom duration: An individual participant data meta-analysis from the OA trial bank 症状持续时间短的膝骨关节炎患者比症状持续时间长的患者更容易从运动疗法中获益：来自 OA 试验库的个体参与者数据荟萃分析。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-18 DOI: 10.1016/j.joca.2024.07.007

M. van Middelkoop , D. Schiphof , M. Hattle , J. Simkins , K.L. Bennell , R.S. Hinman , K.D. Allen , J. Knoop , M.E. van Baar , D. Bossen , J. Wallis , M. Hurley , M.A. Holden , S.M.A. Bierma-Zeinstra

Objective

To investigate whether duration of knee symptoms influenced the magnitude of the effect of exercise therapy compared to non-exercise control interventions on pain and physical function in people with knee osteoarthritis (OA).

Method

We undertook an individual participant data (IPD) meta-analysis utilising IPD stored within the OA Trial Bank from randomised controlled trials (RCTs) comparing exercise to non-exercise control interventions among people with knee OA. IPD from RCTs were analysed to determine the treatment effect by considering both study-level and individual-level covariates in the multilevel regression model. To estimate the interaction effect (i.e., treatment x duration of symptoms (dichotomised)), on self-reported pain or physical function (standardised to 0–100 scale), a one-stage multilevel regression model was applied.

Results

We included IPD from 1767 participants with knee OA from 10 RCTs. Significant interaction effects between the study arm and symptom duration (≤1 year vs >1 year, and ≤2 years vs>2 years) were found for short- (∼3 months) (Mean Difference (MD) −3.57, 95%CI −6.76 to −0.38 and −4.12, 95% CI-6.58 to −1.66, respectively) and long-term (∼12 months) pain outcomes (MD −8.33, 95%CI −12.51 to −4.15 and −8.00, 95%CI −11.21 to −4.80, respectively), and long-term function outcomes (MD −5.46, 95%CI −9.22 to −1.70 and −4.56 95%CI −7.33 to-1.80, respectively).

Conclusions

This IPD meta-analysis demonstrated that people with a relatively short symptom duration benefit more from therapeutic exercise than those with a longer symptom duration. Therefore, there seems to be a window of opportunity to target therapeutic exercise in knee OA.

目的研究膝关节症状持续时间是否会影响运动疗法与非运动对照干预对膝关节骨性关节炎（OA）患者疼痛和身体功能的影响程度：我们利用 OA 试验库（OA Trial Bank）中存储的个人参与者数据（IPD）进行了荟萃分析，这些数据来自随机对照试验（RCT），对膝关节 OA 患者进行了运动与非运动对照干预的比较。通过在多层次回归模型中考虑研究水平和个体水平的协变量，对来自随机对照试验的IPD进行分析，以确定治疗效果。为了估计交互效应（即治疗 x 症状持续时间（二分法））对自我报告疼痛或身体功能（标准化为 0-100 分）的影响，我们采用了单阶段多层次回归模型：我们纳入了来自 10 项研究性临床试验的 1767 名膝关节 OA 患者的 IPD。研究臂和症状持续时间（≤1年 vs >1年，≤2年 vs >2年）之间的显著交互效应在短期（约3个月）（平均差（MD）分别为-3.57，95%CI -6.76至-0.38和-4.12，95%CI-6.58至-1.66）和长期（约3个月）（平均差（MD）分别为-3.57，95%CI -6.76至-0.38和-4.12，95%CI-6.58至-1.66）被发现。66）和长期（约12个月）疼痛结果（MD分别为-8.33，95%CI为-12.51至-4.15和-8.00，95%CI为-11.21至-4.80），以及长期功能结果（MD分别为-5.46，95%CI为-9.22至-1.70和-4.56，95%CI为-7.33至-1.80）：这项IPD荟萃分析表明，与症状持续时间较长的患者相比，症状持续时间较短的患者从治疗性运动中获益更多。因此，针对膝关节 OA 的治疗性运动似乎存在机会之窗。

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引用次数: 0

Development of a core domain set for ankle osteoarthritis: An international consensus study of patients and health professionals 踝关节骨关节炎核心领域集的开发：患者和医疗专业人员的国际共识研究。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-17 DOI: 10.1016/j.joca.2024.07.004

Sultan Ayyadah Alanazi , Bill Vicenzino , Christiaan J.A. van Bergen , David J. Hunter , Erik A. Wikstrom , Hylton B. Menz , Yvonne M. Golightly , Michelle D. Smith , Core Domain Set for Ankle Osteoarthritis Consensus group

Objectives

To develop an internationally agreed-upon core domain set for ankle osteoarthritis (OA).

Methods

In a three-part Delphi process, a group of multidisciplinary health professionals with expertise in ankle OA and people with ankle OA responded to online questionnaires. The questionnaires proposed a list of 29 candidate domains derived from a systematic review of ankle OA research, and interviews with people with ankle OA and health professionals. Consensus was defined a priori as ≥70% agreement in people with ankle OA and health professionals whether a domain should or should not be included in a core domain set. An online consensus meeting was held to discuss and resolve undecided candidate domains.

Results

A total of 100 people (75 health professionals and 25 people with ankle OA) from 18 countries (4 continents) participated in this study. Five domains reached consensus for inclusion in a core domain set for ankle OA – pain severity, health-related quality of life, function, disability and ankle range of motion. Twenty-one candidate domains reached agreement not to be included in the core domain set, and three domains remained undecided (ankle instability, physical capacity, and mental health).

Conclusion

This international consensus study, which included people with ankle OA and health professionals, has established a core domain set for ankle OA with five domains that should be measured and reported in all ankle OA trials – pain severity, health-related quality of life, function, disability and ankle range of motion. This core domain set will guide the reporting of outcomes in clinical trials on ankle OA. Future research should determine which outcome measurement instruments should be used to measure each of the core domains.

目的：为踝关节骨关节炎（OA）制定一套国际公认的核心领域：为踝关节骨关节炎（OA）制定一套国际公认的核心领域：在一个由三部分组成的德尔菲过程中，一组具有踝关节 OA 方面专业知识的多学科医疗专业人士和踝关节 OA 患者对在线问卷做出了回答。调查问卷提出了一份 29 个候选领域的清单，这些领域来自于对踝关节 OA 研究的系统回顾，以及对踝关节 OA 患者和医疗专业人员的访谈。共识的先验定义是，踝关节OA患者和医疗专业人员对某一领域是否应纳入核心领域集的共识度≥70%：共有来自 18 个国家（4 大洲）的 100 人（75 名医疗专业人员和 25 名踝关节 OA 患者）参与了这项研究。有五个领域达成了纳入踝关节 OA 核心领域集的共识：疼痛严重程度、与健康相关的生活质量、功能、残疾和踝关节活动范围。21个候选领域达成共识，不纳入核心领域集，3个领域仍未确定（踝关节不稳定性、体能和心理健康）：这项国际共识研究包括了踝关节 OA 患者和医疗专业人员，它确立了踝关节 OA 核心领域集，所有踝关节 OA 试验都应测量和报告这五个领域--疼痛严重程度、与健康相关的生活质量、功能、残疾和踝关节活动范围。该核心领域集将指导踝关节 OA 临床试验结果的报告。未来的研究应确定应使用哪些结果测量工具来测量每个核心领域。

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引用次数: 0

The impact of an illness perception conversation on open-label placebo response in knee osteoarthritis: A randomised controlled trial 疾病认知谈话对膝关节骨性关节炎开放标签安慰剂反应的影响：随机对照试验

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-17 DOI: 10.1016/j.joca.2024.07.005

Elisabeth Ginnerup-Nielsen , Tanja Schjødt Jørgensen , Camilla Dew-Hattens , Robin Christensen , Johannes Iuel Berg , Lene Vase , Anna Døssing , Sabrina Mai Nielsen , Lars Erik Kristensen , Henning Bliddal , Karen Ellegaard , Marius Henriksen

Objective

To compare the effect of an illness perception conversation (IPC), relative to a research participation conversation (RPC), on 2-week changes in knee pain in patients with knee osteoarthritis.

Method

This was a randomised single-blind trial. Patients were randomised to two matched conversations. An IP conversation concerning the participant’s knee pain-related illness perception (IP) or an RPC concerning the participant’s motivation for participating in research. Both conversations were followed by an open-label intraarticular saline injection in the most symptomatic knee. The primary outcome was change in knee pain from baseline to 2 weeks follow-up on a 100 mm visual analogue scale (VAS). Key secondary outcomes included the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales: Activities of daily living (ADL) and Quality of life (QoL). Main analyses were based on the intention-to-treat population using repeated measures mixed effects linear models.

Results

103 patients were randomised to the IPC group (n = 52) and the RPC group (n = 51). VAS knee pain scores changed statistically significantly from baseline to end of treatment in both groups, −13.7 (standard error [SE]: 3.2) in the IPC group and −13.0 (SE: 3.1) in the RPC group with an adjusted between-group difference of −0.7 (95% CI: −8.3 to 6.9; P = 0.85). Likewise, no group differences were seen in KOOS ADL and KOOS QoL.

Conclusion

A conversation concerning knee pain-related IP did not augment the pain-relieving effect of an open-label placebo injection when compared to a similar control conversation concerning motivations for participating in research.

Trial registration

NCT05225480.

目的比较疾病认知对话（IPC）与研究参与对话（RPC）对膝关节骨性关节炎患者膝关节疼痛两周变化的影响：这是一项随机单盲试验。患者被随机分配到两个匹配的对话中。疾病认知（IP）对话，涉及参与者与膝关节疼痛相关的疾病认知；研究参与对话，涉及参与者参与研究的动机。两次对话后，在症状最严重的膝关节内注射开放标签的关节内生理盐水。主要结果是膝关节疼痛从基线到随访 2 周的变化，采用 100 毫米视觉模拟量表（VAS）。主要次要结果包括膝关节损伤和骨关节炎结果评分（KOOS）分量表：日常生活活动 (ADL) 和生活质量 (QoL)。主要分析基于意向治疗人群，采用重复测量混合效应线性模型：103名患者被随机分配到IPC组（n = 52）和RPC组（n = 51）。从基线到治疗结束，两组患者的 VAS 膝关节疼痛评分均有显著的统计学变化，IPC 组为-13.7（SE：3.2），RPC 组为-13.0（SE：3.1），调整后的组间差异为-0.7（95% CI：-8.3 至 6.9；P= 0.85）。同样，在 KOOS ADL 和 KOOS QoL 方面也未发现组间差异：结论：与关于参与研究动机的类似对照对话相比，与膝关节疼痛相关的IP对话并不能增强开放标签安慰剂注射的止痛效果：试验注册：NCT05225480。

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引用次数: 0

Letter to Editor regarding article ‘Cost and outcomes of Hospital-based Usual cAre versus Tele-monitor self-directed Rehabilitation (HUATR) in patients with total knee arthroplasty: A randomized, controlled, non-inferiority trial’ 致编辑的信，内容涉及 "全膝关节置换术患者的医院惯常康复（HUATR）与远程监控自我指导康复（HUATR）的成本和疗效：随机对照、非劣效试验 "一文。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-15 DOI: 10.1016/j.joca.2024.07.002

Jiahua Zhang, Yuhan Gong, Xinjie Wang

引用次数: 0

Response to Letter to the Editor: ‘Cost and outcomes of Hospital-based Usual cAre versus Tele-monitor self-directed Rehabilitation (HUATR) in patients with total knee arthroplasty: A randomized, controlled, non-inferiority trial’ 回应致编辑的信："全膝关节置换术患者的医院惯常康复（HUATR）与远程监控自主康复（HUATR）的成本和疗效：随机对照、非劣效试验"。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-14 DOI: 10.1016/j.joca.2024.07.003

Yong-Hao Pua , John Wei-Ming Tan

引用次数: 0

Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging 通过 X 射线或磁共振成像确定骨关节炎患者在接受法舒单抗临床试验筛查前存在关节骨病变的患病率。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-14 DOI: 10.1016/j.joca.2024.07.001

Stephen J. DiMartino , Haitao Gao , Tuhina Neogi , Thomas Fuerst , Souhil Zaim , Simon Eng , Tina Ho , Garen Manvelian , Ned Braunstein , Gregory P. Geba , Paula Dakin

Objective

To examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials.

Method

This post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren–Lawrence grade (KLG) ≥ 2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥ 3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported.

Results

Of 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥ 1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.60%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.13% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays.

Conclusions

Approximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.

目的研究参加法舒单抗临床试验的骨关节炎（OA）所致髋关节或膝关节疼痛患者中已有关节骨病变的患病率：这项事后分析包括为三项法舒单抗三期研究（NCT02683239、NCT03161093和NCT03304379）筛选的OA患者。在筛选过程中，符合其他临床纳入/排除标准的参与者接受了膝关节、髋关节和肩关节的放射线检查。指数关节Kellgren-Lawrence分级（KLG）≥2且无排除性发现的患者将接受指数关节、对侧关节和KLG≥3关节的磁共振成像（MRI）检查。排除性检查结果包括 X 光或核磁共振检查发现的骨破碎/塌陷、骨丢失/吸收、骨坏死和骨折。患有广泛软骨下囊肿的参与者也被排除在外。结果：在接受筛查的 27,633 名参与者中，21,997 人接受了成像检查。其中，1203 人（5.5%）因存在≥1 个关节的严重关节骨病变（X 光片或 MRI）而被排除在外：骨碎裂/塌陷（2.61%）、软骨下不全骨折（SIF；1.67%）、骨坏死（1.11%）和明显骨质流失（0.32%）。此外，3.14%的筛查失败者是由于广泛的软骨下囊肿。半数以上因骨破碎/塌陷（386/572）、骨坏死（141/245）和明显骨质流失（59/71）而被排除，约三分之一的SIF（133/367）和广泛软骨下囊肿（229/689）在X光片上表现明显：结论：大约每20名符合法舒单抗3期临床筛选标准的OA患者中就有一人因X光或核磁共振检查发现已有严重的关节骨病变而被排除在外。

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引用次数: 0

Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury 白细胞介素受体治疗剂可减轻犬十字韧带损伤后滑膜的炎症反应。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-14 DOI: 10.1016/j.joca.2024.06.010

Elisabeth A. Lemmon , Kevin G. Burt , Sung Yeon Kim , Bryan Kwok , Lorielle Laforest , Rui Xiao , Lin Han , Carla R. Scanzello , Robert L. Mauck , Kimberly A. Agnello

Objective

In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis.

Design

Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n = 10/group) and micromechanical testing (n = 5/group) to identify changes in tissue architecture and stiffness. Additional samples (n = 5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n = 6 (IL1) or n = 8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6).

Results

Cruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators.

Conclusion

Spontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.

目的：膝关节韧带损伤后的滑膜纤维化与渐进性关节疼痛和僵硬有关。本研究旨在评估犬自然发生十字韧带损伤后滑膜结构、机械性能和转录特征的变化，并测试针对滑膜炎症和纤维化驱动因素的潜在疗法：设计：通过组织学（n=10/组）和微机械测试（n=5/组）评估犬自发性十字韧带撕裂的滑膜和健康膝关节的滑膜，以确定组织结构和硬度的变化。对其他样本（5 个/组）进行 RNA 测序，以确定转录对损伤的反应。最后，对受伤动物的滑膜组织样本（n=6（IL1）或n=8（IL6）/组）进行体外评估，以确定其对针对白细胞介素（IL）信号传导的治疗分子（IL1或IL6）的反应：结果：十字韧带损伤导致滑膜纤维化、血管扩张、炎性细胞浸润和内膜增生加剧。此外，与健康组织相比，病变组织内膜和内膜下区域的硬度更高。差异基因表达分析表明，病变滑膜的免疫反应和细胞粘附通路上调，Rho蛋白转导通路下调。体外应用靶向IL1（anakinra）或IL6（tocilizumab）的小分子疗法抑制了炎症和基质沉积介质的表达：结论：犬自发性十字韧带损伤与滑膜炎症和纤维化有关，是测试新出现的关节内治疗方法的相关模型。针对 IL 通路的小分子疗法可能是损伤后向关节间隙输送药物的理想干预措施。

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引用次数: 0

Evaluation of circulating microRNA signature in patients with erosive hand osteoarthritis: The HOAmiR study 评估侵蚀性手部骨关节炎患者的循环 microRNA 特征：HOAmiR 研究。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-08 DOI: 10.1016/j.joca.2024.06.017

Objectives

To identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA.

Methods

In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI).

Results

In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196–5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA.

After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis.

Conclusions

We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.

目的与非侵蚀性手部骨关节炎（HOA）患者和无HOA患者相比，确定侵蚀性手部骨关节炎（HOA）患者循环中表达不同的微RNA：在筛选阶段，使用 Taqman 低密度阵列卡对 10 名侵蚀性手部骨关节炎患者、10 名非侵蚀性手部骨关节炎患者和 10 名未患手部骨关节炎的对照组的 30 份血清中的 768 种特征明确的微 RNA 进行了检测，这些患者的年龄和体重指数与对照组相匹配。第二步，我们在更大的样本（年龄和体重指数匹配的 60 名侵蚀性 HOA 患者和 60 名非 HOA 患者）中验证了筛查阶段发现的微 RNA（使用 Benjamini-Hochberg 方法和文献综述校正误发现率后，调整后的 p 值小于 0.05）：在筛选阶段，我们在侵蚀性 HOA 和对照组之间发现了 21 个下调和 4 个上调的相关微 RNA。其中，9 个微 RNA（miR-373-3p、miR-558、miR-607、miR-653-5p、miR-137 和 miR448 下调，miR-142-3p、miR-144-3p 和 miR-34a-5p 上调）以前在软骨细胞平衡或 OA 中被描述过。我们发现，在侵蚀性 HOA 和非侵蚀性 HOA 之间，只有一种微 RNA 明显下调。在验证阶段，我们重复了先前在筛查阶段发现的侵蚀性 HOA 患者与非侵蚀性 HOA 患者相比，miR-196-5p 明显下调的单一微 RNA。在查阅文献和miRNA-基因相互作用预测模型后，我们发现该microRNA可与骨稳态和HOXC8相互作用，这可以解释其在骨关节炎中的作用：我们发现，miR-196-5p 在侵蚀性 HOA 患者中被下调，而它的一些靶点可解释其在 OA 中的作用。

{"title":"Evaluation of circulating microRNA signature in patients with erosive hand osteoarthritis: The HOAmiR study","authors":"","doi":"10.1016/j.joca.2024.06.017","DOIUrl":"10.1016/j.joca.2024.06.017","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA.</div></div><div><h3>Methods</h3><div>In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI).</div></div><div><h3>Results</h3><div><span>In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes<span> homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant </span></span>downregulation of miR-196–5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA.</div><div>After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis<span> and HOXC8, which could explain its role in osteoarthritis.</span></div></div><div><h3>Conclusions</h3><div>We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1452-1462"},"PeriodicalIF":7.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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