Osteoarthritis and Cartilage最新文献_第7页

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。

{"title":"The impact of an illness perception conversation on open-label placebo response in knee osteoarthritis: A randomised controlled trial","authors":"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","doi":"10.1016/j.joca.2024.07.005","DOIUrl":"10.1016/j.joca.2024.07.005","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Method</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div><div><h3>Trial registration</h3><div>NCT05225480.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 12","pages":"Pages 1610-1619"},"PeriodicalIF":7.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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。

{"title":"Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging","authors":"Stephen J. DiMartino , Haitao Gao , Tuhina Neogi , Thomas Fuerst , Souhil Zaim , Simon Eng , Tina Ho , Garen Manvelian , Ned Braunstein , Gregory P. Geba , Paula Dakin","doi":"10.1016/j.joca.2024.07.001","DOIUrl":"10.1016/j.joca.2024.07.001","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Method</h3><div>This <em>post-hoc</em> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 12","pages":"Pages 1601-1609"},"PeriodicalIF":7.2,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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。

{"title":"Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury","authors":"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","doi":"10.1016/j.joca.2024.06.010","DOIUrl":"10.1016/j.joca.2024.06.010","url":null,"abstract":"<div><h3>Objective</h3><p>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.</p></div><div><h3>Design</h3><p>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).</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 10","pages":"Pages 1295-1307"},"PeriodicalIF":7.2,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616978","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}

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}

引用次数: 0

Associations between static foot posture, dynamic in-shoe plantar foot forces and knee pain in people with medial knee osteoarthritis: A cross-sectional exploratory study 膝关节内侧骨关节炎患者的静态足部姿势、动态鞋内足底力与膝关节疼痛之间的关系：一项横断面探索性研究。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-08 DOI: 10.1016/j.joca.2024.04.023

Objective

To investigate relationships between static foot posture, dynamic plantar foot forces and knee pain in people with medial knee osteoarthritis (OA).

Design

Data from 164 participants with symptomatic, moderate to severe radiographic medial knee OA were analysed. Knee pain was self-reported using a numerical rating scale (NRS; scores 0–10; higher scores worse) and the Knee Injury and Osteoarthritis Outcome Score pain subscale (KOOS; scores 0–100; lower scores worse). Static foot posture was assessed using clinical tests (foot posture index, foot mobility magnitude, navicular drop). Dynamic plantar foot forces (lateral, medial, whole foot, medial-lateral ratio, arch index) were measured using an in-shoe plantar pressure system while walking. Relationships between foot posture and plantar forces (independent variables) and pain (dependent variables) were evaluated using linear regression models, unadjusted and adjusted for sex, walking speed, Kellgren & Lawrence grade, shoe category, and body mass (for dynamic plantar foot forces).

Results

No measure of static foot posture was associated with any knee pain measure. Higher medial-lateral foot force ratio at midstance, and a higher arch index during overall stance, were weakly associated with higher knee pain on the NRS (regression coefficient = 0.69, 95% confidence interval (CI) 0.09 to 1.28) and KOOS (coefficient=3.03, 95% CI 0.71 to 5.35) pain scales, respectively.

Conclusion

Dynamic plantar foot forces, but not static foot posture, were associated with knee pain in people with medial knee OA. However, the amount of pain explained by increases in plantar foot force was small; thus, these associations are unlikely to be clinically meaningful.

目的研究膝关节内侧骨关节炎（OA）患者的足部静态姿势、足底动态力量和膝关节疼痛之间的关系：分析了 164 名有症状、中度至重度膝关节内侧骨性关节炎放射学检查参与者的数据。膝关节疼痛采用数字评分量表（NRS；0-10分；越高越严重）和膝关节损伤和骨关节炎结果评分疼痛子量表（KOOS；0-100分；越低越严重）进行自我报告。足部静态姿势通过临床测试（足部姿势指数、足部活动度大小、舟状突下降）进行评估。步行时使用鞋内足底压力系统测量足底动态压力（外侧、内侧、全足、内外侧比率、足弓指数）。使用线性回归模型评估了足部姿势和足底压力（自变量）与疼痛（因变量）之间的关系，未对性别、行走速度、KL等级、鞋子类别和体重（动态足底压力）进行调整：结果：足部静态姿势的测量结果与膝关节疼痛的测量结果均无关联。在NRS（回归系数=0.69，95%置信区间（CI）为0.09至1.28）和KOOS（系数=3.03，95%置信区间（CI）为0.71至5.35）疼痛量表中，中段站立时较高的足内外侧力比率和整体站立时较高的足弓指数分别与较高的膝关节疼痛呈弱相关：结论：膝关节内侧OA患者的膝关节疼痛与足底动态力量有关，而与足部静态姿势无关。然而，足底力量的增加所能解释的疼痛程度很小，因此这些关联不太可能具有临床意义。

{"title":"Associations between static foot posture, dynamic in-shoe plantar foot forces and knee pain in people with medial knee osteoarthritis: A cross-sectional exploratory study","authors":"","doi":"10.1016/j.joca.2024.04.023","DOIUrl":"10.1016/j.joca.2024.04.023","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate relationships between static foot posture, dynamic plantar foot forces and knee pain in people with medial knee osteoarthritis (OA).</p></div><div><h3>Design</h3><p>Data from 164 participants with symptomatic, moderate to severe radiographic medial knee OA were analysed. Knee pain was self-reported using a numerical rating scale (NRS; scores 0–10; higher scores worse) and the Knee Injury and Osteoarthritis Outcome Score pain subscale (KOOS; scores 0–100; lower scores worse). Static foot posture was assessed using clinical tests (foot posture index, foot mobility magnitude, navicular drop). Dynamic plantar foot forces (lateral, medial, whole foot, medial-lateral ratio, arch index) were measured using an in-shoe plantar pressure system while walking. Relationships between foot posture and plantar forces (independent variables) and pain (dependent variables) were evaluated using linear regression models, unadjusted and adjusted for sex, walking speed, Kellgren & Lawrence grade, shoe category, and body mass (for dynamic plantar foot forces).</p></div><div><h3>Results</h3><p>No measure of static foot posture was associated with any knee pain measure. Higher medial-lateral foot force ratio at midstance, and a higher arch index during overall stance, were weakly associated with higher knee pain on the NRS (regression coefficient = 0.69, 95% confidence interval (CI) 0.09 to 1.28) and KOOS (coefficient=3.03, 95% CI 0.71 to 5.35) pain scales, respectively.</p></div><div><h3>Conclusion</h3><p>Dynamic plantar foot forces, but not static foot posture, were associated with knee pain in people with medial knee OA. However, the amount of pain explained by increases in plantar foot force was small; thus, these associations are unlikely to be clinically meaningful.</p></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 10","pages":"Pages 1339-1345"},"PeriodicalIF":7.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1063458424012639/pdfft?md5=15d402ad29a362cbd1a0541c7c24f9da&pid=1-s2.0-S1063458424012639-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex differences in patellar facet shape among healthy and osteoarthritic cohorts 健康人群和骨关节炎人群髌骨面形状的性别差异。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-08 DOI: 10.1016/j.joca.2024.06.018

Objective

Patellofemoral osteoarthritis (OA) may be more common in females than males. Reasons for this are not fully understood, but sex differences in patellar morphology may help explain this phenomenon. We quantified differences in patellar morphology between males and females in healthy and patellofemoral OA populations.

Design

A total of 97 (50F, 47M) healthy and 67 (40F, 27M) OA knees were scanned via computed tomography. OA individuals were on a waitlist for total knee replacement. Patella 3D models were segmented and 2D measurements were recorded: patellar width and height, lateral and medial facet width, and surface area. Medial and lateral facet surface topography was mapped using 81 points to describe 3D articular surface shape. Sex and group differences were assessed using Procrustes analysis of variance (ANOVA). Data were ordinated using Principal Component Analysis.

Results

Differences in patellar 2D measurements between healthy and OA individuals were smaller than were differences between males and females from healthy and OA groups. Sex and healthy/OA differences were most pronounced for medial facet shape, which featured a posteriorly-curving facet and taller, narrower facet shape in males compared to females. Lateral facet shape variance was higher in OA cohorts compared to healthy groups.

Conclusions

Medial and lateral facet shapes showed different patterning of variation by sex and healthy/OA status. Lateral facet shape may be of interest in future models of OA risk in the patellofemoral joint, here showing increased magnitudes of variance associated with increased severity of disease (patellofemoral Kellgren and Lawrence score).

目的：髌骨骨关节炎（OA）在女性中可能比男性更常见。其原因尚不完全清楚，但髌骨形态的性别差异可能有助于解释这一现象。我们对健康人群和髌骨OA人群中男性和女性髌骨形态的差异进行了量化。设计：通过计算机断层扫描对97个（50F，47M）健康膝关节和67个（40F，27M）OA膝关节进行了扫描。OA患者正在等待进行全膝关节置换术。对髌骨三维模型进行分割，并记录二维测量结果：髌骨宽度和高度、外侧和内侧切面宽度以及表面积。使用 81 个点绘制内侧和外侧面表面地形图，以描述三维关节面形状。使用 Procrustes 方差分析评估性别和组别差异。使用主成分分析法对数据进行排序：结果：健康人和 OA 患者之间的髌骨二维测量差异小于健康组和 OA 组男性和女性之间的差异。内侧髌面形状的性别差异和健康/OA差异最为明显，男性髌面向后弯曲，髌面形状比女性高而窄。与健康人群相比，OA人群的外侧切面形状差异更大：结论：内侧和外侧切面形状因性别和健康/OA状态的不同而呈现出不同的变化模式。外侧切面形状在未来的髌股关节OA风险模型中可能会受到关注，其变异幅度随疾病严重程度（髌股关节KL评分）的增加而增加。

{"title":"Sex differences in patellar facet shape among healthy and osteoarthritic cohorts","authors":"","doi":"10.1016/j.joca.2024.06.018","DOIUrl":"10.1016/j.joca.2024.06.018","url":null,"abstract":"<div><h3>Objective</h3><div>Patellofemoral osteoarthritis (OA) may be more common in females than males. Reasons for this are not fully understood, but sex differences in patellar morphology may help explain this phenomenon. We quantified differences in patellar morphology between males and females in healthy and patellofemoral OA populations.</div></div><div><h3>Design</h3><div>A total of 97 (50F, 47M) healthy and 67 (40F, 27M) OA knees were scanned via computed tomography. OA individuals were on a waitlist for total knee replacement. Patella 3D models were segmented and 2D measurements were recorded: patellar width and height, lateral and medial facet width, and surface area. Medial and lateral facet surface topography was mapped using 81 points to describe 3D articular surface shape. Sex and group differences were assessed using Procrustes analysis of variance (ANOVA). Data were ordinated using Principal Component Analysis.</div></div><div><h3>Results</h3><div>Differences in patellar 2D measurements between healthy and OA individuals were smaller than were differences between males and females from healthy and OA groups. Sex and healthy/OA differences were most pronounced for medial facet shape, which featured a posteriorly-curving facet and taller, narrower facet shape in males compared to females. Lateral facet shape variance was higher in OA cohorts compared to healthy groups.</div></div><div><h3>Conclusions</h3><div>Medial and lateral facet shapes showed different patterning of variation by sex and healthy/OA status. Lateral facet shape may be of interest in future models of OA risk in the patellofemoral joint, here showing increased magnitudes of variance associated with increased severity of disease (patellofemoral Kellgren and Lawrence score).</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1433-1442"},"PeriodicalIF":7.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study 膝关节骨性关节炎晚期滑膜组织损伤与疼痛之间的关系：一项横断面研究。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-04 DOI: 10.1016/j.joca.2024.06.015

Objective

To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA).

Design

In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates.

Results

Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (−1.47 [95%CI −2.88, −0.05]), even while adjusting for synovial inflammation (−1.61 [95%CI −3.12, −0.10]).

Conclusions

Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

目的确定滑膜炎症和组织损伤的组织病理学特征的存在和分布情况，并检验它们与膝关节骨性关节炎（OA）滑膜炎的 US 成像测量值和患者报告的疼痛测量值之间的关联：在对122名因晚期（Kellgren-Lawrence 3级或4级）膝关节OA疼痛而接受手术的患者进行的横断面研究中，我们比较了滑膜炎（118人）和疼痛（膝关节损伤和骨关节炎结果评分）的超声（US）测量值与滑膜组织活检中炎症与滑膜组织损伤的组织病理学测量值。采用线性或逻辑回归评估组织病理学特征与美国炎症或疼痛测量值之间的关联，同时控制协变量：结果：炎症组织病理学特征与中度/重度US滑膜炎的较高几率相关（OR=1.34 [95%CI 1.04, 1.74]），而滑膜组织损伤特征与中度/重度US滑膜炎的较低几率相关（OR=0.77 [95%CI 0.57, 1.03]）。滑膜组织损伤的组织病理学评分越差，疼痛感越强（-1.47 [95%CI -2.88，-0.05]），即使对滑膜炎症进行调整（-1.61 [95%CI -3.12，-0.10]）也是如此：结论：滑膜组织损伤与膝关节OA晚期疼痛有关，与炎症和影像学损伤无关。这些新发现表明，预防滑膜组织损伤可能是改变疾病的 OA 治疗的一个重要目标。

{"title":"Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study","authors":"","doi":"10.1016/j.joca.2024.06.015","DOIUrl":"10.1016/j.joca.2024.06.015","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA).</div></div><div><h3>Design</h3><div>In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates.</div></div><div><h3>Results</h3><div>Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (−1.47 [95%CI −2.88, −0.05]), even while adjusting for synovial inflammation (−1.61 [95%CI −3.12, −0.10]).</div></div><div><h3>Conclusions</h3><div>Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 11","pages":"Pages 1503-1512"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery ACL 重建手术后早期微 RNA 和代谢物的变化

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-07-04 DOI: 10.1016/j.joca.2024.06.013

Objectives

Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA’s natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males.

Methods

A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed.

Results

Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log₂-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log₂-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log₂-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log₂-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males.

Conclusion

MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.

目标：前交叉韧带（ACL）损伤后的重建并不能预防创伤后骨关节炎（PTOA）。前交叉韧带损伤和重建后不久出现的循环微核糖核酸（miRNA）和代谢物变化仍未得到充分定义，它们可能是导致创伤后骨关节炎演变的早期线索。此外，它们在女性和男性之间的不同表达也可能影响 PTOA 的自然轨迹。本研究旨在确定前交叉韧带重建后早期阶段女性和男性血浆 miRNA 和代谢物水平的变化：方法：对 43 名前交叉韧带重建患者进行了研究。方法：研究人员对 43 名前交叉韧带重建患者进行了研究，分别在基线、术后 2 周和 6 周采集血浆（共 129 份生物样本）。进行了高通量 miRNA 测序和代谢组学研究。采用负二项式和线性回归模型分别鉴定了差异表达的 miRNA 和代谢物。以时间和性别为共同变量（手术前与手术后 2 周和 6 周），探讨了 miRNA 与代谢物之间的关联。利用计算生物学方法，进行了 miRNA-代谢物-基因相互作用和通路分析：结果：通过 miRNA 测序，46 个 miRNA 的水平在手术后 2 周比手术前（基线）有所提高。利用代谢组学，与基线相比，13 种代谢物的水平在手术后 2 周明显升高，而 6 种代谢物的水平在手术后 2 周明显降低。与男性相比，女性受试者在手术后 2 周（log2-fold-change 0.71，95%CI 0.22,1.20）和 6 周（log2-fold-change 0.75，95%CI 0.07,1.43）的 Hsa-miR-145-5p 水平均有所上升。此外，女性的 hsa-miR-497-5p 水平在手术后 2 周（log2-fold-change 0.77，95%CI 0.06,1.48）和 6 周（log2-fold-change 0.83，95%CI 0.07,1.59）均有所增加。与男性相比，女性在手术后 2 周内有五种代谢物减少：L-亮氨酸（-1.44，95%CI -1.75,-1.13）、g-鸟苷酸丁酸盐（-1.27，95%CI 1.54,-0.99）、肌酐（-1.17，95%CI -1.44,-0.90）、2-甲基丁酰肉碱（-1.76，95%CI -2.17,-1.35）和leu-pro（-1.13，95%CI -1.44,-0.83）。MiRNA-代谢物-基因相互作用分析揭示了基于手术后时间点以及女性与男性的关键信号通路：结论：前交叉韧带重建手术后早期，MiRNA和代谢物谱随时间和性别而改变，这可能会影响手术反应，并最终影响罹患PTOA的风险。

{"title":"Early microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery","authors":"","doi":"10.1016/j.joca.2024.06.013","DOIUrl":"10.1016/j.joca.2024.06.013","url":null,"abstract":"<div><h3>Objectives</h3><p>Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA’s natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males.</p></div><div><h3>Methods</h3><p>A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed.</p></div><div><h3>Results</h3><p>Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log<sub>2</sub>-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log<sub>2</sub>-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log<sub>2</sub>-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log<sub>2</sub>-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males.</p></div><div><h3>Conclusion</h3><p>MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.</p></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"32 9","pages":"Pages 1113-1125"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1063458424012664/pdfft?md5=a4e6ccc01b0bc6569d57da1ff8b8e88d&pid=1-s2.0-S1063458424012664-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0