Osteoarthritis and Cartilage最新文献

英文中文

Protein Folding Dependence on Selenoprotein M Contributes to Steady Cartilage Extracellular Matrix Repressing Ferroptosis Via PERK/ATF4/CHAC1 Axis. 蛋白折叠对硒蛋白 M 的依赖有助于通过 PERK/ATF4/CHAC1 轴稳定软骨细胞外基质以抑制铁凋亡

IF 7 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-10-15 DOI: 10.1016/j.joca.2024.10.005

Yitong Zhao,Ying Zheng,Han Li,Yao Li,Ru Wang,Yongsong Cai,Haishi Zheng,Xinyu Huo,Jiajun Ren,Dongxian Guo,Rui Luo,Xinyao Wu,Jingyi Lu,Qingxin Song,Yan Zhang,Chenxing Ma,Lu Wang,Runyuan Wang,Jing Wang,Yingli He,Peng Xu,Jian Sun,Shemin Lu

OBJECTIVEInitiation of endoplasmic reticulum (ER) stress is pivotal to the advancement of osteoarthritis (OA). We aimed to explore the function of ER-resident selenoprotein M (SELM) in cartilage-forming chondrocytes, investigating how SELM participates in cartilage extracellular matrix (ECM) metabolism and ER stress modulation.METHODSArticular cartilage samples with knee OA undergoing total knee arthroplasty were categorized into OA-smooth and OA-damaged groups, with primary chondrocytes extracted from smooth areas. Destabilization of the medial meniscus was induced in male C57BL6/J mice, with sham operations on the left knee as controls. After 8 weeks, knee joint tissues were collected for analysis. Histology and immunohistochemistry examined cartilage damage. Molecular biology techniques investigated how SELM affects ECM metabolism and ER stress regulation. RNA sequencing revealed the pathway changes after SELM intervention. AlphaFold demonstrated how SELM interacts with other molecules. Cultured cartilage explants helped determine the effects of SELM supplementation.RESULTSSELM expression was reduced in the damaged cartilage. Increasing SELM levels positively impacted ECM equilibrium. Decreasing SELM expression activated genes linked to degenerative ailments and impaired the cellular response to misfolded proteins, initiating the PERK/P-EIF2A/ATF4 pathway and exacerbating GSH/GSSG imbalance via the ATF4/CHAC1 axis. SELM likely participated in protein folding and modification by leveraging its thioredoxin domains. In vitro SELM supplementation mitigated IL-1β effects on damaged cartilage explants and suppressed beneficial chondrocyte phenotypes.CONCLUSIONSOur results confirm the involvement of SELM in ER stress-induced cartilage damage as well as protein folding, pointing to new directions in molecular therapy for degenerative diseases.

目的内质网（ER）应激是导致骨关节炎（OA）的关键因素。我们旨在探索ER驻留硒蛋白M（SELM）在软骨形成软骨细胞中的功能，研究SELM如何参与软骨细胞外基质（ECM）的新陈代谢和ER应激调节。诱导雄性 C57BL6/J 小鼠内侧半月板失稳，以左膝假手术作为对照。8 周后，收集膝关节组织进行分析。组织学和免疫组化检查软骨损伤情况。分子生物学技术研究了SELM如何影响ECM代谢和ER应激调节。RNA测序揭示了SELM干预后的通路变化。AlphaFold显示了SELM如何与其他分子相互作用。培养软骨外植体有助于确定补充SELM的效果。提高SELM水平对ECM平衡有积极影响。SELM表达的减少激活了与退行性疾病相关的基因，损害了细胞对错误折叠蛋白的反应，启动了PERK/P-EIF2A/ATF4途径，并通过ATF4/CHAC1轴加剧了GSH/GSSG失衡。SELM可能通过利用其硫代毒素结构域参与蛋白质折叠和修饰。体外补充 SELM 可减轻 IL-1β 对受损软骨外植体的影响，并抑制有益的软骨细胞表型。

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引用次数: 0

Making sense of osteoarthritis: A narrative review. 了解骨关节炎：叙事性综述。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-10-09 DOI: 10.1016/j.joca.2024.09.012

Ben Darlow, Joletta Belton, Melanie Brown, Jane Clark, Dawn P Richards, Naomi Simick Behera, Samantha Bunzli

People make sense of osteoarthritis (OA) by drawing on information, beliefs, and knowledge. This narrative review summarises diverse qualitative and quantitative research investigating beliefs and knowledge about OA and the impact these have on behaviour and outcomes. It synthesises evidence and highlights key actions clinicians can take to support people to make sense of OA in helpful ways. Beliefs about OA inform the behaviour of those living with OA and the behaviour of clinicians caring for people with OA. Beliefs about OA often focus on joint degradation and inevitable progression. These impairment-focused fatalistic beliefs can result in reduced offer of, or engagement in, active management strategies. Alternative views focus on health as part of a dynamic ecosystem where people are healthy when they can participate in activities they value. These beliefs are associated with increased engagement in self-management and lifestyle-based interventions. Clinician actions that support people to make sense of OA ways that align with helpful behaviours and support participation in valued activities represent key opportunities to improve health and well-being.

人们通过信息、信念和知识来理解骨关节炎（OA）。这篇叙述性综述总结了有关OA信念和知识的各种定性和定量研究，以及这些信念和知识对行为和结果的影响。它综合了相关证据，并强调了临床医生可以采取的关键行动，以支持人们以有益的方式了解 OA。对OA的信念影响着OA患者的行为和护理OA患者的临床医生的行为。对OA的信念通常集中在关节退化和不可避免的进展上。这些以损伤为重点的宿命论信念会导致主动管理策略的提供或参与度降低。另一种观点则将健康视为动态生态系统的一部分，当人们能够参与他们所珍视的活动时，他们就是健康的。这些观念与更多人参与自我管理和基于生活方式的干预措施有关。临床医生采取的行动能够帮助人们理解 OA，使其与有益的行为保持一致，并支持人们参与有价值的活动，这些行动是改善健康和福祉的关键机会。

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引用次数: 0

Emerging Evidence of Artemin/GFRα3 Signaling in Musculoskeletal Pain. 肌肉骨骼疼痛中青蒿素/GFRα3 信号传递的新证据

IF 7 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-10-05 DOI: 10.1016/j.joca.2024.09.010

Ankita Gupta,Santosh K Mishra,B Duncan X Lascelles

Chronic musculoskeletal pain is highly prevalent and poses a significant personal, societal, and economic burden. Management of chronic musculoskeletal pain remains a challenge. Long-term use of common analgesic medications such as nonsteroidal anti-inflammatory drugs and opioids is associated with adverse events, and in the case of opioids, drug addiction. Additionally, many individuals do not experience sufficient pain relief with these therapeutic approaches. Thus, there is an urgent need to develop clinically efficacious and safe therapeutics for musculoskeletal pain. Recent advances in our understanding of musculoskeletal pain neurobiology have helped identify the role of neurotrophic factors, specifically, the GDNF Family of Ligands (GFL) and their associated signaling pathways. This review outlines our current understanding of the GFL signaling systems, discusses their role in inflammatory and chronic musculoskeletal pain and sensitivity, and comments on the analgesic therapeutic potential of targeting the GFL signaling system.

慢性肌肉骨骼疼痛发病率很高，给个人、社会和经济造成了沉重负担。慢性肌肉骨骼疼痛的治疗仍然是一项挑战。长期使用非甾体抗炎药和阿片类药物等常见镇痛药物会导致不良反应，阿片类药物还会导致药物成瘾。此外，许多人在使用这些治疗方法后疼痛并没有得到充分缓解。因此，开发临床上有效且安全的肌肉骨骼疼痛治疗方法迫在眉睫。最近，我们对肌肉骨骼疼痛神经生物学的认识取得了进展，这有助于确定神经营养因子的作用，特别是 GDNF 家族配体（GFL）及其相关信号通路。这篇综述概述了我们目前对 GFL 信号系统的理解，讨论了它们在炎症和慢性肌肉骨骼疼痛及敏感性中的作用，并评论了靶向 GFL 信号系统的镇痛治疗潜力。

引用次数: 0

Osteoarthritis year in review 2024: Biomechanics 骨关节炎 2024 年回顾：生物力学。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-10-04 DOI: 10.1016/j.joca.2024.09.011

Annegret Mündermann , Corina Nüesch , Hannah Ewald , Ilse Jonkers

Objective

We aimed to systematically review and summarize the literature of the past year on osteoarthritis (OA) and biomechanics, to highlight gaps and challenges, and to present some promising approaches and developments.

Methods

A systematic literature search was conducted using Pubmed and the Web of Science Core Collection. We included original articles and systematic reviews on OA and biomechanics in human subjects published between April 2023 and April 2024.

Results

Of the 155 studies that met the inclusion criteria, 9 were systematic reviews and 146 were original (mostly cross-sectional) studies that included a total of 6488 patients and 1921 controls with a mean age of 57.5 and 44.7 years, respectively. Promising advances have been made in medical imaging of affected soft tissue structures, the relationship between soft tissue properties and biomechanical changes in OA, new technologies to facilitate easier assessment of ambulatory biomechanics, and personalized physics-based models that also include complex chemical and mechanobiological mechanisms, all of which are relevant to gaining mechanistic insights into the pathophysiology of OA.

Conclusions

There is still an unmet need for larger longitudinal data sets that combine clinical, radiological, and biomechanical outcomes to characterize the biomechanical fingerprint that underlies the trajectory of functional decline and biomechanical phenotypes of OA. In addition, criteria and guidelines for control groups, as well as methods and standards for model verification allowing for comparisons between studies are needed.

目的我们旨在系统回顾和总结过去一年有关 OA 和生物力学的文献，突出差距和挑战，并介绍一些有前景的方法和发展：使用 Pubmed 和 Web of Science Core Collection 进行了系统的文献检索。我们纳入了 2023 年 4 月至 2024 年 4 月间发表的关于人体 OA 和生物力学的原创文章和系统综述：结果：在符合纳入标准的 155 项研究中，9 项为系统综述，146 项为原创（大部分为横断面）研究，共纳入 6488 名患者和 1921 名对照者，平均年龄分别为 57.5 岁和 44.7 岁。受影响软组织结构的医学成像、OA 中软组织特性与生物力学变化之间的关系、便于评估非卧床生物力学的新技术以及基于物理学的个性化模型（其中还包括复杂的化学和机械生物学机制）等方面都取得了可喜的进展，所有这些都有助于从机理上深入了解 OA 的病理生理学：目前仍然需要结合临床、放射学和生物力学结果的更大规模的纵向数据集，以描述支撑 OA 功能衰退轨迹和生物力学表型的生物力学指纹。此外，还需要制定对照组的标准和指南，以及模型验证的方法和标准，以便在不同研究之间进行比较。

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引用次数: 0

What if OA cartilage degradation is driven by the infrapatellar fat pad? Insights from lipodystrophy models. 如果OA软骨降解是由髌下脂肪垫驱动的？脂肪营养不良模型的启示

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-10-02 DOI: 10.1016/j.joca.2024.09.007

Lea Loisay, Xavier Houard

引用次数: 0

Cartilage on the test bench - What is the functional role of synovial fluid in reducing wear and fatigue? 试验台上的软骨--滑液在减少磨损和疲劳方面的功能作用是什么？

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-10-02 DOI: 10.1016/j.joca.2024.09.009

Markus A Wimmer, Thomas M Schmid

引用次数: 0

Assessment of whole cartilage surface damage in an osteoarthritis rat model: The Cartilage Roughness Score (CRS) utilizing microcomputed tomography. 骨关节炎大鼠模型中整体软骨表面损伤的评估：利用微计算机断层扫描的软骨粗糙度评分（CRS）。

IF 7.2 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-09-30 DOI: 10.1016/j.joca.2024.09.008

Sami Kauppinen, David Fercher, Gonçalo Barreto, Ville-Pauli Karjalainen, Vesa Virtanen, Lucia Baixauli-Marin, Marina Fonti, Shipin Zhang, Tuomas Frondelius, Patrick Weber, Simo Saarakkala, Marcy Zenobi-Wong, Mikko A J Finnilä

Objective: This study aims to establish an accurate and robust imaging biomarker for pre-clinical osteoarthritis (OA) research, focusing on early detection of cartilage surface degeneration.

Method: Using 50 male Wistar rats, this study aims to observe Collagenase-induced OA (CIOA) progression through microcomputed x-ray tomography (µCT), histopathological analysis, and gait analysis. A novel parameter, Cartilage Roughness Score (CRS), was developed for assessing cartilage structural damage from µCT data and was compared with histological OARSI Cartilage Degeneration Score (OARSI CDS). Additionally, as CRS maps the full surface, it was used to simulate the level of uncertainty in histological sampling.

Results: CRS and OARSI CDS have a linear relationship. CRS for healthy cartilage is 2.75 (95% CI: 1.14-4.36), and with every 1 unit increase in OARSI, CRS is expected to increase by 0.64 (95% CI: 0.35-0.92). Cartilage degeneration due to CIOA was evident in both histopathological scoring and CRS. However, only CRS was sensitive enough to show consistent damage progression from day 10 to day 60. Furthermore, our simulation for histological sampling suggested that up to 16 coronal slices with 200 µm spacing would be needed to accurately represent the full extent of cartilage surface degeneration in a slice-wise manner. Gait analysis showed changes solely at eight days post-collagenase injection, normalizing by day 60.

Conclusion: The CRS analysis method emerges as a robust tool for cartilage surface damage assessment. This study demonstrates the potential of automatic 3D analysis over the traditional 2D histological approach when evaluating cartilage surface damage.

研究目的本研究旨在为临床前骨关节炎（OA）研究建立一种准确、可靠的成像生物标志物，重点是早期检测软骨表面退化：本研究使用50只雄性Wistar大鼠，通过微计算机X射线断层成像（µCT）、组织病理学分析和步态分析，观察胶原酶诱导的骨关节炎（CIOA）的进展。研究人员开发了一种新参数--软骨粗糙度评分（CRS），用于根据μCT数据评估软骨结构损伤，并与组织病理学OARSI软骨退化评分（OARSI CDS）进行了比较。此外，由于CRS映射的是整个表面，因此可用于模拟组织学取样的不确定性水平：结果：CRS 和 OARSI CDS 呈线性关系。健康软骨的 CRS 为 2.75（95% CI：1.14-4.36），OARSI 每增加 1 个单位，CRS 预计增加 0.64（95% CI：0.35-0.92）。在组织病理学评分和 CRS 中，CIOA 导致的软骨退化都很明显。然而，只有 CRS 的灵敏度足以显示从第 10 天到第 60 天的持续损伤进展。此外，我们对组织学取样的模拟显示，要以切片的方式准确反映软骨表面退化的全部程度，需要多达16张间距为200微米的冠状切片。步态分析显示，只有在注射胶原酶后八天，步态才会发生变化，到第60天步态趋于正常：CRS分析方法是评估软骨表面损伤的有力工具。这项研究表明，在评估软骨表面损伤时，自动三维分析比传统的二维组织学方法更有潜力：微计算机断层扫描数据可通过ida.fairdata.fi46 (https://doi.org/10.23729/f33d3ba8-01b8-47af-90dd-94b7c7861247)获取。

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引用次数: 0

When ‘synovitis’ is not synovitis 当 "滑膜炎 "不是滑膜炎时

IF 7 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-09-23 DOI: 10.1016/j.joca.2024.09.005

Sung Yeon Kim, Carla R. Scanzello

引用次数: 0

Cracking the Pericellular Matrix Code: Exploring How MMP-2, -3, and -7 Influence Matrix Breakdown and Biomechanical Properties. 破解细胞周基密码：探索 MMP-2、-3 和 -7 如何影响基质分解和生物力学特性。

IF 7 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-09-23 DOI: 10.1016/j.joca.2024.09.006

Benjamin Tizian Baumann,Jule Nieuwstraten,Christian Konrads,Farshid Guilak,Marina Danalache

INTRODUCTIONThe intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.METHODSHuman articular cartilage explants (N=10 patients) were incubated with activated MMP-2, -3, or -7, individually or in combination. Structural alterations in the PCM were evaluated by immunolabeling. The biomechanical properties of the PCM were measured using atomic force microscopy (AFM).RESULTSCollagen type VI structural integrity and fluorescence intensity uniformly decreased across all enzyme groups, while perlecan was selectively affected by MMP-3 and -7. AFM measurements demonstrated decreased PCM stiffness after incubation with individual MMPs, leading to an overall ~31 % reduction in elastic modulus for each enzyme. Combinations of enzymes induced comparable significant biomechanical alterations (~35 %), except for MMP-2+MMP-7.DISCUSSIONThis study highlights the significant influence of MMP-induced alterations in PCM composition on biomechanical properties, mirroring characteristics observed in early OA. Each MMP showed specificity in breaking down PCM, and an intriguing interplay, especially between MMP-2 and -7, indicated reduced efficacy in lowering PCM stiffness. Overall, MMP-2, -3, and -7 directly induce functional and structural PCM modifications.

引言关节软骨重塑的过程错综复杂，对其生理功能和骨关节炎（OA）的发展都至关重要，这一过程是通过基质金属蛋白酶（MMPs）介导的基质合成和分解平衡来协调的。这种重塑的核心是细胞外基质（PCM），它是一种包裹每个软骨细胞的特殊微环境，主要由 VI 型胶原蛋白和perlecan 组成。本研究的目的是评估 MMP-2、-3 和 -7 对 PCM 结构完整性和生物力学属性的影响。方法将人类关节软骨外植体（N=10 名患者）与活化的 MMP-2、-3 或 -7 单独或混合培养。通过免疫标记评估 PCM 的结构变化。结果六型胶原的结构完整性和荧光强度在所有酶组中一致下降，而过氧化物酶则受到 MMP-3 和 -7 的选择性影响。 AFM 测量显示，与单个 MMP 培养后，PCM 的硬度下降，导致每种酶的弹性模量总体下降约 31%。除 MMP-2+MMP-7 外，酶的组合诱导了类似的显著生物力学改变（~35%）。每种 MMP 在分解 PCM 时都表现出特异性，尤其是 MMP-2 和 -7 之间的相互作用耐人寻味，这表明它们在降低 PCM 硬度方面的功效减弱。总体而言，MMP-2、-3 和 -7 可直接诱导 PCM 的功能和结构改变。

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Degradomics defines proteolysis information flow from human knee osteoarthritis cartilage to matched synovial fluid and the contributions of secreted proteases ADAMTS5, MMP13 and CMA1 to articular cartilage breakdown 降解组学定义了从人类膝关节骨关节炎软骨到匹配滑液的蛋白水解信息流，以及分泌蛋白酶 ADAMTS5、MMP13 和 CMA1 对关节软骨破坏的贡献

IF 7 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2024-09-16 DOI: 10.1016/j.joca.2024.09.002

Sumit Bhutada, Anna Hoyle, Nicolas S. Piuzzi, Suneel S. Apte

Proteolytic cartilage extracellular matrix breakdown is a major mechanism of articular cartilage loss in osteoarthritis (OA) pathogenesis. We sought to determine the overlap of proteolytic peptides in matched knee OA cartilage and synovial fluid on a proteome-wide scale to increase the prospective biomarker repertoire and to attribute proteolytic cleavages to specific secreted proteases.

蛋白水解软骨细胞外基质分解是骨关节炎（OA）发病机制中关节软骨损失的主要机制。我们试图确定匹配的膝关节OA软骨和滑膜液中的蛋白水解肽在整个蛋白质组范围内的重叠情况，以增加前瞻性生物标志物库，并将蛋白水解裂解归因于特定的分泌蛋白酶。

引用次数: 0

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