Osteoarthritis and Cartilage最新文献_第9页

Contextualizing unnormalized vertical ground reaction force and knee osteoarthritis: Association does not imply mechanical causation 情境化非标准化垂直地面反作用力与膝关节OA：关联并不意味着机械因果关系。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-10-01 DOI: 10.1016/j.joca.2025.09.017

Karl Morgan

引用次数: 0

Age- and sex-specific knee alignment patterns in symptomatic Korean patients: A cross-sectional deep learning analysis of 16,000 knees 有症状的韩国患者的年龄和性别特异性膝关节排列模式：对16,000个膝关节的横断面深度学习分析。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.joca.2025.10.011

Hong-Seon Lee , Se-Han Jung , Seung-hyun Song , Chaeri Park , Young Han Lee , Sung-Hwan Kim , Sangchul Hwang , Sungjun Kim

Objective

To analyze age- and sex-specific associations in knee alignment using a large dataset of long-leg radiographs with deep learning-based automated measurements.

Methods

This retrospective cross-sectional study included 8014 radiographs (16,028 knees) from symptomatic adults who underwent long-leg radiography at a tertiary hospital in South Korea (2010–2023). Alignment parameters, including mechanical tibiofemoral angle (MTFA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA), were automatically extracted using a deep learning model. Linear regression assessed age-related associations stratified by sex and age group (<50 years versus ≥50 years), adjusting for body mass index, Kellgren–Lawrence grade, and clinical indication.

Results

After adjustment, age-related associations in knee alignment differed by sex and age group. MTFA increased with age, most prominently in women aged ≥50 years (right/left β = 0.053/0.040 degrees per year, 95% CI 0.038–0.068/0.025–0.054, whereas the association was minimal in men aged ≥50 years (right/left β = –0.006/0.001, 95% CI –0.026–0.014/-0.018–0.021). LDFA was positively associated with age among participants < 50 years, but showed no clear association thereafter. MPTA decreased with age in younger men and women, while remaining near zero or slightly positive in older groups. JLCA increased with age in participants ≥ 50 years, particularly in women.

Conclusion

Knee alignment demonstrated nonlinear associations with age and clear sex-related differences. These findings underscore the need to consider age- and sex-specific alignment characteristics in clinical evaluation and research on osteoarthritis risk.

目的：利用基于深度学习的自动测量的长腿x线片数据集，分析年龄和性别特异性与膝关节对齐的关联。方法：本回顾性横断面研究包括2010-2023年在韩国一家三级医院接受长腿x线摄影的有症状成人的8014张x线片（16028个膝关节）。利用深度学习模型自动提取胫骨股骨机械角（MTFA）、股骨外侧远端角（LDFA）、胫骨内侧近端角（MPTA）和关节线收敛角（JLCA）等对准参数。线性回归评估了按性别和年龄组（<50岁vs≥50岁）分层的年龄相关关联，调整了体重指数、kelgren - lawrence分级和临床适应症。结果调整后，不同性别和年龄组的膝关节对齐的年龄相关性存在差异。MTFA随着年龄的增长而增加，在≥50岁的女性中最为显著（右/左β = 0.053/0.040度/年，95% CI 0.038-0.068/0.025-0.054），而在≥50岁的男性中相关性最小（右/左β = -0.006/0.001, 95% CI -0.026-0.014/-0.018-0.021）。在< 50岁的参与者中，LDFA与年龄呈正相关，但此后无明显相关性。MPTA在年轻男性和女性中随着年龄的增长而下降，而在老年人群中保持接近零或略呈阳性。在≥50岁的参与者中，JLCA随年龄增长而增加，尤其是女性。结论膝关节线形与年龄呈非线性相关，性别差异明显。这些发现强调了在骨关节炎风险的临床评估和研究中考虑年龄和性别特异性排列特征的必要性。

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引用次数: 0

Response to letter to the editor regarding ‘The relation of walking forces to structural damage in the knee: The Multicenter Osteoarthritis Study’ 关于“步行力与膝关节结构损伤的关系：多中心骨关节炎研究”致编辑的回复

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-11-19 DOI: 10.1016/j.joca.2025.11.006

Lauren K. Sara, David T. Felson, Michael P. LaValley, Joshua J. Stefanik, Cara L. Lewis

引用次数: 0

Acknowledgement to Reviewers 2024-2025 对审稿人的致谢2024-2025

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2026-01-06 DOI: 10.1016/j.joca.2025.12.011

D. Hunter Editor in Chief, A.-M. Malfait Editor in Chief

引用次数: 0

Dampened inflammation and reduced risk of osteoarthritis among non-industrialized societies 在非工业化社会中抑制炎症和降低骨关节炎的风险。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-10-08 DOI: 10.1016/j.joca.2025.09.014

Ian J. Wallace , David T. Felson , Virginia B. Kraus , Tuhina Neogi , Ida K. Haugen , Janet L. Huebner , Cecilia M.T. Sena , Tracy L. Kivell , Nicholas B. Holowka , Steven Worthington , Yvonne A.L. Lim , Vivek V. Venkataraman , Thomas S. Kraft , Amanda J. Lea

Objectives

Anthropological research suggests that people in non-industrialized societies (hunter-gatherers, subsistence farmers, pastoralists) are at lower risk of osteoarthritis than people in industrialized societies. Here, we propose that this may be due to people in non-industrialized societies having dampened inflammatory activity, a key factor in osteoarthritis pathogenesis.

Design

This narrative review focuses on evidence that four environmental variables common among non-industrialized societies contribute to dampening inflammatory activity and thus potentially lowering OA risk: low levels of adiposity, high physical activity levels, diets consisting of minimally processed foods, and infections from helminths.

Results

Although people in non-industrialized societies experience intermittent, pathogen-induced spikes in inflammation, they do not typically experience the chronic, low-grade pattern of inflammation implicated in osteoarthritis pathogenesis. Excess adipose tissue is well documented to be a potent source of pro-inflammatory mediators involved in osteoarthritis pathogenesis; thus, the rarity of obesity among non-industrialized societies is likely a major reason for any reduced osteoarthritis risk. Physical activity and diet among non-industrialized societies have the potential to curb inflammation and osteoarthritis through several mechanistic pathways, yet the relative importance of each pathway has yet to be fully resolved. A role for helminths in dampening inflammation and lowering OA risk is theoretically plausible but speculative based on current evidence.

Conclusions

More research among non-industrialized societies will be required to rigorously investigate the links proposed here between industrialization, inflammation, and risk of osteoarthritis. Opportunities to do so are disappearing, as lifestyles among such societies are rapidly changing.

目的人类学研究表明，非工业化社会（狩猎采集者、自给自足的农民、牧民）的人患骨关节炎的风险低于工业化社会的人。在这里，我们提出这可能是由于非工业化社会的人们抑制了炎症活动，这是骨关节炎发病的一个关键因素。本叙述性综述的重点是在非工业化社会中常见的四个环境变量有助于抑制炎症活动，从而潜在地降低OA风险的证据：低脂肪水平、高体力活动水平、由最低加工食品组成的饮食和蠕虫感染。结果：尽管非工业化社会的人们会经历间歇性的、病原体引起的炎症峰值，但他们通常不会经历与骨关节炎发病机制有关的慢性、低度炎症模式。多余的脂肪组织被充分证明是参与骨关节炎发病的促炎介质的有力来源；因此，在非工业化社会中，肥胖的罕见可能是降低骨关节炎风险的主要原因。在非工业化社会中，体育活动和饮食有可能通过几种机制途径抑制炎症和骨关节炎，但每种途径的相对重要性尚未得到充分解决。蠕虫在抑制炎症和降低OA风险方面的作用在理论上是合理的，但基于目前的证据是推测性的。结论需要在非工业化社会中进行更多的研究，以严格调查工业化、炎症和骨关节炎风险之间的联系。这样做的机会正在消失，因为这些社会的生活方式正在迅速改变。

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引用次数: 0

Osteoarthritis year in review 2025: Imaging 骨关节炎年回顾2025：影像学。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1016/j.joca.2025.11.004

Matthew S. Harkey , Anthony A. Gatti , Mylène P. Jansen , McKenzie S. White , Jessica Tolzman , Arjun Parmar , Ian Frederick , Thomas M. Link , Harvi F. Hart

Objective

To conduct a narrative review of selected imaging studies published in the past year, with a focus on how emerging methods and multi-tissue assessments are contributing to disease characterization, early detection, and intervention strategies.

Design

We conducted a comprehensive search strategy of PubMed, Embase, and CINAHL for original English-language human studies on imaging in osteoarthritis, published between March 2024 and March 2025. From the 262 full-text studies that met inclusion criteria, we identified a set of representative studies through independent review and group discussion. These studies are organized into five themes that emerged from this study: effusion-synovitis, infrapatellar fat pad, muscle, subchondral bone, and subcutaneous fat. Within each theme, one highlighted study and several additional studies were synthesized, followed by a summary of cross-cutting insights and future directions.

Results

A total of 26 studies were included. Collectively, the studies reinforce the importance of viewing osteoarthritis as a condition involving multiple joint structures, with inflammation as a recurring feature across tissues. Muscle quality and local adiposity emerged as consistent imaging biomarkers, while accessible tools such as ultrasound and AI-enhanced radiography demonstrated potential for scalable clinical application. Links between imaging findings and biomechanics, particularly gait and loading patterns, also featured prominently. Cross-cutting themes emphasized the value of considering multiple tissues, expanding the reach of imaging to clinical and community settings, and integrating imaging with functional measures.

Conclusions

Imaging research in the osteoarthritis continues to broaden in scope and application. The studies highlighted in this review illustrate how advances in methods and metrics are improving opportunities for earlier detection, more precise assessment of symptoms, and the development of targeted, structure-informed interventions.

目的对过去一年中发表的精选影像学研究进行综述，重点关注新兴方法和多组织评估如何有助于疾病表征、早期发现和干预策略。我们对PubMed， Embase和CINAHL进行了全面的搜索策略，以获取在2024年3月至2025年3月之间发表的关于骨关节炎成像的原始英语人类研究。从符合纳入标准的262项全文研究中，我们通过独立审查和小组讨论确定了一组具有代表性的研究。这些研究被分为五个主题：积液-滑膜炎、髌下脂肪垫、肌肉、软骨下骨和皮下脂肪。在每个主题中，综合了一个重点研究和几个附加研究，然后总结了交叉见解和未来方向。结果共纳入26项研究。总的来说，这些研究强调了将骨关节炎视为一种涉及多个关节结构的疾病的重要性，炎症是组织中反复出现的特征。肌肉质量和局部肥胖成为一致的成像生物标志物，而超声和人工智能增强放射照相等可获得的工具显示出可扩展临床应用的潜力。成像结果与生物力学之间的联系，特别是步态和负荷模式，也很突出。交叉主题强调了考虑多种组织的价值，将成像范围扩大到临床和社区环境，并将成像与功能测量相结合。结论骨关节炎影像学研究的范围和应用不断拓宽。本综述中强调的研究说明了方法和指标的进步如何改善了早期发现的机会，更精确地评估症状，并开发了有针对性的、结构知情的干预措施。

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引用次数: 0

Same pain, different brainstem: Sex-dependent astrocytic activation in the rostral ventromedial medulla during experimental osteoarthritis 相同的疼痛，不同的脑干：实验性骨关节炎期间吻侧腹内侧髓质中性别依赖的星形细胞激活。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-10-17 DOI: 10.1016/j.joca.2025.10.006

Diana Fonseca-Rodrigues , Inês Laranjeira , Luiz Falconi-Sobrinho , Juliana Fiúza-Fernandes , Beatriz Soares , Luísa Pinto , Filipa Pinto-Ribeiro

Objective

Osteoarthritis (OA) is the leading cause of chronic pain worldwide. Functional studies showed a critical role of descending facilitation, involving the rostral ventromedial medulla (RVM), in the establishment of pain chronicity. Glial cells such as microglia and astrocytes can contribute to chronic pain through the facilitation of neuronal excitability. This work aimed to characterize the morpho-structural changes in the RVM induced by experimental OA (eOA) pain and to identify potential sexual dimorphisms.

Methods

The kaolin/carrageenan model of eOA was induced in 23 male and 22 female Wistar Han rats. Four weeks later, brain samples were collected and divided into two analyses: stereological evaluation of changes in neuronal/glial cell density within the RVM, and immunohistochemical analysis of glial activation, astrocyte proliferation and structural changes.

Results

While no major differences were found in the RVM volume or area, osteoarthritic females exhibited a higher glia-to-neuron ratio (95%CI: 0.13–0.76; p=0.006), driven by increased glial cell density. A significant increase in GFAP-positive cells was observed in females (95%CI: 1.95–25.8; p=0.025), without a corresponding increase in Iba1 immunoreactivity, an effect not seen in males. Increased mitotic activity and structural complexity of astrocytes in osteoarthritic females were further confirmed by immunofluorescence and Sholl analysis, respectively.

Conclusions

Our findings highlight the intricate relationship between eOA-related pain and the RVM cellular dynamics, revealing sex-specific astrocyte activation following eOA and its potential role in the mediation pain processing and chronification. These results suggest targeting astrocyte-mediated mechanisms as potential sex-specific therapeutic strategy for OA pain management.

目的骨关节炎（OA）是世界范围内慢性疼痛的主要原因。功能研究表明，下行促进作用，包括吻侧腹内侧延髓（RVM），在疼痛慢性的建立中起关键作用。神经胶质细胞如小胶质细胞和星形胶质细胞可以通过促进神经元兴奋性来促进慢性疼痛。这项工作旨在表征实验性OA （eOA）疼痛引起的RVM形态结构变化，并确定潜在的性别二态性。方法采用高岭土/卡拉胶法制备23只雄性Wistar Han大鼠和22只雌性Wistar Han大鼠eOA模型。4周后，收集脑样本，分为两个分析：RVM内神经元/胶质细胞密度变化的体视学评估，以及胶质细胞激活、星形胶质细胞增殖和结构变化的免疫组织化学分析。结果虽然RVM的体积和面积没有明显差异，但骨性关节炎女性由于胶质细胞密度增加，胶质细胞与神经元的比例更高（95%CI: 0.13-0.76; p=0.006）。在女性中观察到gfap阳性细胞显著增加（95%CI: 1.95-25.8; p=0.025），而Iba1免疫反应性未相应增加，这在男性中未见。免疫荧光和Sholl分析进一步证实了骨关节炎女性星形细胞有丝分裂活性和结构复杂性的增加。结论我们的研究结果强调了eOA相关疼痛与RVM细胞动力学之间的复杂关系，揭示了eOA后性别特异性星形胶质细胞激活及其在介导疼痛加工和慢性化中的潜在作用。这些结果表明，针对星形胶质细胞介导的机制是OA疼痛管理的潜在性别特异性治疗策略。

{"title":"Same pain, different brainstem: Sex-dependent astrocytic activation in the rostral ventromedial medulla during experimental osteoarthritis","authors":"Diana Fonseca-Rodrigues , Inês Laranjeira , Luiz Falconi-Sobrinho , Juliana Fiúza-Fernandes , Beatriz Soares , Luísa Pinto , Filipa Pinto-Ribeiro","doi":"10.1016/j.joca.2025.10.006","DOIUrl":"10.1016/j.joca.2025.10.006","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis (OA) is the leading cause of chronic pain worldwide. Functional studies showed a critical role of descending facilitation, involving the rostral ventromedial medulla (RVM), in the establishment of pain chronicity. Glial cells such as microglia and astrocytes can contribute to chronic pain through the facilitation of neuronal excitability. This work aimed to characterize the morpho-structural changes in the RVM induced by experimental OA (eOA) pain and to identify potential sexual dimorphisms.</div></div><div><h3>Methods</h3><div>The kaolin/carrageenan model of eOA was induced in 23 male and 22 female Wistar Han rats. Four weeks later, brain samples were collected and divided into two analyses: stereological evaluation of changes in neuronal/glial cell density within the RVM, and immunohistochemical analysis of glial activation, astrocyte proliferation and structural changes.</div></div><div><h3>Results</h3><div>While no major differences were found in the RVM volume or area, osteoarthritic females exhibited a higher glia-to-neuron ratio (95%CI: 0.13–0.76; p=0.006), driven by increased glial cell density. A significant increase in GFAP-positive cells was observed in females (95%CI: 1.95–25.8; p=0.025), without a corresponding increase in Iba1 immunoreactivity, an effect not seen in males. Increased mitotic activity and structural complexity of astrocytes in osteoarthritic females were further confirmed by immunofluorescence and Sholl analysis, respectively.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the intricate relationship between eOA-related pain and the RVM cellular dynamics, revealing sex-specific astrocyte activation following eOA and its potential role in the mediation pain processing and chronification. These results suggest targeting astrocyte-mediated mechanisms as potential sex-specific therapeutic strategy for OA pain management.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 70-81"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319249","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

Filler advert: knovel_210x280.pdf 填充广告：knovel_210x280.pdf

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2026-01-06 DOI: 10.1016/S1063-4584(25)01284-1

引用次数: 0

A decade of exposure: Long-term air pollution and its impact on osteoarthritis: A nationwide cohort study in Taiwan 十年暴露：长期空气污染及其对骨关节炎的影响：台湾一项全国性队列研究。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-05-09 DOI: 10.1016/j.joca.2025.04.011

Yi-Chuan Chan , Yen-Wei Huang , Shu-Han Chuang , Yi-Jie Kuo , Yu-Pin Chen

Objective

To investigate the association between long-term exposure to ambient air pollution and the risk of developing osteoarthritis (OA) in a large nationwide cohort in Taiwan.

Design

We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database linked with air pollution monitoring records from 76 environmental stations between 1993 and 2013. A total of 526,630 adults with complete 10-year cumulative exposure data were followed from the end of the exposure window until OA diagnosis, death, or study end. Cox proportional hazards models were applied to estimate hazard ratios (HRs) per standard deviation (SD) increase in pollutant exposure, adjusting for demographic, socioeconomic, and clinical confounders. Pollutants that satisfied the proportional hazards assumption (carbon monoxide [CO], particles less than 10 μm in diameter [PM₁₀], and nitrogen dioxide [NO₂]) were included in the final analysis to ensure model validity.

Results

During follow-up, 58,369 incident OA cases were identified (11.08% incidence). A 1 SD increase in CO, PM₁₀, and NO₂ exposure was associated with HRs of 1.83 (95% confidence interval: 1.81–1.84), 1.58 (1.56–1.60), and 1.62 (1.61–1.64), respectively (all p < 0.001). These associations were robust across sex subgroups and exhibited consistent dose-response relationships.

Conclusions

We observed a significant association between prolonged exposure to CO, PM₁₀, and NO₂ and increased OA risk. These findings support air pollution as a modifiable risk factor for OA and highlight the importance of environmental health interventions in disease prevention strategies.

目的探讨台湾地区长期暴露于环境空气污染与患骨关节炎（OA）风险的关系。从暴露窗口结束到OA诊断、死亡或研究结束，共有526,630名具有完整10年累积暴露数据的成年人接受了随访。Cox比例风险模型用于估计污染物暴露每标准差（SD）增加的风险比（hr），并对人口统计学、社会经济和临床混杂因素进行调整。满足比例危害假设的污染物（CO、PM₁₀和NO₂）被纳入最终分析，以确保模型的有效性。结果随访共发现OA 58,369例，发生率11.08%。CO， PM₁0和NO₂暴露增加1个标准差与hr分别为1.83 (95% CI: 1.81-1.84), 1.58（1.56-1.60）和1.62（1.61-1.64）相关（均p < 0.001）。这些关联在性别亚组中都很明显，并表现出一致的剂量-反应关系。结论：我们观察到长期暴露于CO、PM 1 0和NO 2与OA风险增加之间存在显著关联。这些发现支持空气污染是OA的一个可改变的风险因素，并强调了环境卫生干预在疾病预防战略中的重要性。

{"title":"A decade of exposure: Long-term air pollution and its impact on osteoarthritis: A nationwide cohort study in Taiwan","authors":"Yi-Chuan Chan , Yen-Wei Huang , Shu-Han Chuang , Yi-Jie Kuo , Yu-Pin Chen","doi":"10.1016/j.joca.2025.04.011","DOIUrl":"10.1016/j.joca.2025.04.011","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the association between long-term exposure to ambient air pollution and the risk of developing osteoarthritis (OA) in a large nationwide cohort in Taiwan.</div></div><div><h3>Design</h3><div><span><span><span>We conducted a retrospective cohort study<span> using data from Taiwan's National Health Insurance Research Database linked with air pollution monitoring records from 76 environmental stations between 1993 and 2013. A total of 526,630 adults with complete 10-year cumulative exposure data were followed from the end of the exposure window until OA diagnosis, death, or study end. Cox proportional hazards models were applied to estimate hazard ratios (HRs) per standard deviation (SD) increase in </span></span>pollutant exposure, adjusting for demographic, socioeconomic, and clinical confounders. Pollutants that satisfied the proportional hazards assumption (carbon monoxide [CO], particles less than 10 μm in diameter [PM₁₀], and </span>nitrogen dioxide [NO</span><sub>2</sub>]) were included in the final analysis to ensure model validity.</div></div><div><h3>Results</h3><div>During follow-up, 58,369 incident OA cases were identified (11.08% incidence). A 1 SD increase in CO, PM₁₀, and NO₂ exposure was associated with HRs of 1.83 (95% confidence interval: 1.81–1.84), 1.58 (1.56–1.60), and 1.62 (1.61–1.64), respectively (all p < 0.001). These associations were robust across sex subgroups and exhibited consistent dose-response relationships.</div></div><div><h3>Conclusions</h3><div>We observed a significant association between prolonged exposure to CO, PM₁₀, and NO₂ and increased OA risk. These findings support air pollution as a modifiable risk factor<span><span> for OA and highlight the importance of environmental health interventions in disease </span>prevention strategies.</span></div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 139-147"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933004","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

Imeglimin, a novel antidiabetic agent related to metformin, attenuates knee osteoarthritis development and progression through AMPK activation and NF-κB signaling inhibition 依米明是一种由二甲双胍合成的新型降糖药物，通过激活AMPK和抑制NF-κB信号传导来减轻膝关节骨性关节炎的发生和进展

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 Epub Date: 2025-11-20 DOI: 10.1016/j.joca.2025.11.007

Yuki Hyodo , Yukio Akasaki , Ichiro Kurakazu , Masanari Kuwahara , Taisuke Uchida , Ryota Hirose , Mamiko Sakai , Takumi Kita , Koki Kato , Yasuharu Nakashima

Objective

Metformin, a first-line treatment for type 2 diabetes, attenuates hallmarks of aging and protects against age-related diseases, including osteoarthritis (OA). Here, we assessed the effects of imeglimin, a novel antidiabetic agent related to metformin, on the development and progression of knee OA.

Design

Primary human OA chondrocytes, synovial cells, and meniscal cells were stimulated with IL-1β and treated with imeglimin (n = 8). OA-related gene and protein expressions were quantified using RT-qPCR and ELISA. Activation of NF-κB and AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, was assessed using western blotting and immunofluorescence. Additionally, we evaluated its efficacy in two knee OA mouse models (n = 10): destabilization of the medial meniscus and medial collateral ligament transection (DMM+MCLT), and monoiodoacetate (MIA)-induced OA pain.

Results

Imeglimin suppressed IL-1β-induced expressions of OA-related genes, including pro-inflammatory (IL6, IL1B, TNF), catabolic (MMP13, ADAMTS5), and pain-related (CCL2, NGF) genes, and reduced IL6 secretion. Western blot analysis revealed downregulation of IκBα and p65 activation and AMPK upregulation. Immunocytochemistry confirmed decreased p65 nuclear translocation (-4245 AU; 95% CI −6765 to −1725). Intra-articular administration of imeglimin reduced histological severity of OA in cartilage, synovium, and meniscus in DMM+MCLT mice (OARSI grade, −3.0 [95% CI: −5.0 to −1.0]), decreased the number of cells expressing p-IκBα in the articular cartilage, and attenuated OA pain in both DMM+MCLT and MIA models.

Conclusions

Imeglimin enhances protective functions in joint tissue cells and alleviates experimental OA in preclinical mouse models, supporting its potential as a therapeutic candidate for knee OA.

目的：甲双胍是2型糖尿病的一线治疗药物，它可以减轻衰老的标志，并预防与年龄相关的疾病，包括骨关节炎（OA）。在这里，我们评估了一种与二甲双胍相关的新型降糖药伊米明对膝关节OA发生和进展的影响。设计：用IL-1β刺激原代人OA软骨细胞、滑膜细胞和半月板细胞，并用伊米霉素处理（n = 8）。采用RT-qPCR和ELISA检测oa相关基因及蛋白的表达。采用western blotting和免疫荧光法检测NF-κB和amp活化蛋白激酶（AMPK）（能量代谢的主要调节因子）的激活情况。此外，我们在两种膝关节OA小鼠模型（n = 10）中评估了其疗效：内侧半月板不稳定和内侧副韧带横断（DMM+MCLT），以及单碘乙酸酯（MIA）诱导的OA疼痛。结果甲米明抑制il -1β诱导的oa相关基因的表达，包括促炎基因（IL6、IL1B、TNF）、分解代谢基因（MMP13、ADAMTS5）和疼痛相关基因（CCL2、NGF），并减少IL6的分泌。Western blot分析显示，IκBα和p65活化下调，AMPK上调。免疫细胞化学证实p65核易位减少（-4245 AU； 95% CI - 6765至- 1725）。在DMM+MCLT和MIA模型中，关节内给药伊米霉素降低了骨性关节炎在软骨、滑膜和半月板的组织学严重程度（OARSI评分为- 3.0 [95% CI: - 5.0至- 1.0]），减少了关节软骨中表达p- κ b α的细胞数量，减轻了骨性关节炎疼痛。结论simeglimin增强了关节组织细胞的保护功能，减轻了临床前小鼠模型的实验性OA，支持其作为治疗膝关节OA的候选药物的潜力。

{"title":"Imeglimin, a novel antidiabetic agent related to metformin, attenuates knee osteoarthritis development and progression through AMPK activation and NF-κB signaling inhibition","authors":"Yuki Hyodo , Yukio Akasaki , Ichiro Kurakazu , Masanari Kuwahara , Taisuke Uchida , Ryota Hirose , Mamiko Sakai , Takumi Kita , Koki Kato , Yasuharu Nakashima","doi":"10.1016/j.joca.2025.11.007","DOIUrl":"10.1016/j.joca.2025.11.007","url":null,"abstract":"<div><h3>Objective</h3><div>Metformin, a first-line treatment for type 2 diabetes, attenuates hallmarks of aging and protects against age-related diseases, including osteoarthritis (OA). Here, we assessed the effects of imeglimin, a novel antidiabetic agent related to metformin, on the development and progression of knee OA.</div></div><div><h3>Design</h3><div>Primary human OA chondrocytes, synovial cells, and meniscal cells were stimulated with IL-1β and treated with imeglimin (n = 8). OA-related gene and protein expressions were quantified using RT-qPCR and ELISA. Activation of NF-κB and AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, was assessed using western blotting and immunofluorescence. Additionally, we evaluated its efficacy in two knee OA mouse models (n = 10): destabilization of the medial meniscus and medial collateral ligament transection (DMM+MCLT), and monoiodoacetate (MIA)-induced OA pain.</div></div><div><h3>Results</h3><div>Imeglimin suppressed IL-1β-induced expressions of OA-related genes, including pro-inflammatory (<em>IL6, IL1B, TNF</em>), catabolic (<em>MMP13</em>, <em>ADAMTS5</em>), and pain-related (<em>CCL2</em>, <em>NGF</em>) genes, and reduced IL6 secretion. Western blot analysis revealed downregulation of IκBα and p65 activation and AMPK upregulation. Immunocytochemistry confirmed decreased p65 nuclear translocation (-4245 AU; 95% CI −6765 to −1725). Intra-articular administration of imeglimin reduced histological severity of OA in cartilage, synovium, and meniscus in DMM+MCLT mice (OARSI grade, −3.0 [95% CI: −5.0 to −1.0]), decreased the number of cells expressing p-IκBα in the articular cartilage, and attenuated OA pain in both DMM+MCLT and MIA models.</div></div><div><h3>Conclusions</h3><div>Imeglimin enhances protective functions in joint tissue cells and alleviates experimental OA in preclinical mouse models, supporting its potential as a therapeutic candidate for knee OA.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 1","pages":"Pages 105-120"},"PeriodicalIF":9.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559846","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