Osteoarthritis and Cartilage最新文献

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IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

Partitioning knee osteoarthritis genetic variants based on BMI association to improve polygenic risk prediction 基于BMI关联划分膝骨关节炎遗传变异以改善多基因风险预测。

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 DOI: 10.1016/j.joca.2025.09.018

Bahar Sedaghati–Khayat , Katerina Trajanoska , Cindy G. Boer , Fernando Rivadeneira , André G. Uitterlinden , Joyce B.J. van Meurs , Jeroen G.J. van Rooij

Introduction

Polygenic risk scores (PRSs) show promise for improving knee osteoarthritis (KOA) risk prediction. However, many KOA-associated variants are also linked to body mass index (BMI)—a major KOA risk factor—complicating the combined use of PRS and BMI in predictive models. This study aimed to disentangle BMI-mediated from BMI-independent genetic contributions to KOA by partitioning the KOA-PRS.

Method

Using data from 345,080 white European participants in the UK Biobank, we refined a KOA-PRS based on 146 genome-wide significant variants identified by the GO consortium. KOA variants were partitioned into BMI-associated (KOA-BMI PRS), and BMI-independent (KOA-nonBMI PRS) groups based on linkage disequilibrium with BMI-associated variants from the GIANT consortium. We assessed associations of each PRS with prevalent and incident KOA (with and without BMI adjustment), with BMI in cases and controls, and with KOA across BMI strata.

Results

Of the 146 KOA-associated variants, 73 were classified as BMI-associated. The KOA-BMI PRS was associated with incident KOA (OR per SD:1.23;95%CI:1.20–1.26), attenuated after BMI adjustment (1.18;1.15–1.21). In contrast, the KOA-nonBMI PRS remained robust to BMI adjustment (1.24 before vs.1.23 after-adjustment). KOA-nonBMI PRS was negatively associated with BMI in KOA cases (β=–0.09;95%CI:–0.17to–0.01), but not in controls. Stratified analyses showed its effect on KOA diminished in higher BMI strata, while KOA-BMI PRS effects remained stable.

Conclusion

Half of KOA-associated variants overlap with BMI loci. Partitioning the KOA-PRS improves interpretation by distinguishing BMI-driven from independent genetic effects—enhancing prediction and informing tailored prevention. Validation in diverse populations is warranted.

多基因风险评分（PRSs）有望改善膝骨关节炎（KOA）的风险预测。然而，许多与KOA相关的变异也与身体质量指数（BMI）有关，这是一个主要的KOA风险因素，使PRS和BMI在预测模型中的联合使用复杂化。本研究旨在通过划分KOA- prs来解开bmi介导的与bmi独立的遗传对KOA的贡献。方法使用来自英国生物银行345,080名欧洲白人参与者的数据，我们基于GO联盟鉴定的146个全基因组显著变异完善了KOA-PRS。根据与GIANT联盟中bmi相关变异的连锁不平衡，将KOA变异分为bmi相关（KOA- bmi PRS）和bmi独立（KOA-非bmi PRS）两组。我们评估了每一种PRS与流行的和偶发的KOA（有和没有BMI调整）、病例和对照组的BMI以及不同BMI层的KOA的关联。结果146例koa相关变异中，73例归为bmi相关。KOA-BMI PRS与KOA事件相关（OR / SD:1.23;95%CI:1.20 ~ 1.26）， BMI调整后减弱（1.18;1.15 ~ 1.21）。相比之下，koa -非BMI PRS对BMI调整保持稳健（调整前为1.24，调整后为1.23）。在KOA病例中，KOA-非BMI PRS与BMI呈负相关（β=-0.09;95%CI:-0.17 -0.01），但在对照组中没有。分层分析表明，高BMI地层对KOA的影响减弱，而KOA-BMI PRS效应保持稳定。结论半数koa相关变异与BMI位点重叠。通过区分bmi驱动和独立的遗传效应，划分KOA-PRS改善了解释，增强了预测，并为量身定制的预防提供了信息。有必要在不同人群中进行验证。

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Response to the Letter to the Editor: Effects of pre- and postsurgery physical activity interventions on physical activity and sedentary behavior levels following knee and hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials 给编辑的回复：术前和术后体育活动干预对膝关节和髋关节置换术后体育活动和久坐行为水平的影响：随机对照试验的系统回顾和荟萃分析

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01 DOI: 10.1016/j.joca.2025.10.013

Noah d’Unienville, Bethany Gower, Ben Singh, Kimberley Szeto, Heather Badger, Matilda Krywanio, Carol Maher , Dominic Thewlis

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 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。

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引用次数: 0

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

IF 9 2区医学 Q1 ORTHOPEDICS

Osteoarthritis and Cartilage

Pub Date : 2026-01-01

引用次数: 0

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