Changes and associations between synovial fluid and magnetic resonance imaging markers of osteoarthritis after high tibial osteotomy

IF 4.9 2区医学 Q1 Medicine

Arthritis Research & Therapy Pub Date : 2024-10-10 DOI:10.1186/s13075-024-03409-3

Jenna M. Schulz, Trevor B. Birmingham, Holly T. Philpott, C. Thomas Appleton, Hayden F. Atkinson, J. Robert Giffin, Frank Beier

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引用次数: 0

Abstract

Mechanobiological mechanisms of osteoarthritis (OA) are unclear. Our objectives were to explore: 1) changes in knee joint physiology using a large panel of synovial fluid biomarkers from before to one year after high tibial osteotomy (HTO) surgery, and 2) the association of changes in the synovial fluid biomarkers with the changes in MRI measures of knee effusion-synovitis and articular cartilage composition. Twenty-six patients with symptomatic knee OA and varus alignment underwent synovial fluid aspirations and 3 T MRI before and one year after medial opening wedge HTO. Cytokine and growth factor levels in synovial fluid were measured with multiplex assays. Ontology and pathway enrichment was assessed using data protein sets with gene set enrichment analysis (GSEA), and analyzed using linear mixed effects models. MRIs were analyzed for effusion-synovitis and T2 cartilage relaxation time using manual segmentations. Changes in biomarker concentrations were correlated to changes in MRI effusion-synovitis volume and articular cartilage T2 relaxation times. Decreased enrichment in Toll-like receptor and TNF-α signalling was detected one year after HTO. The leading contributors to this reduction included IL-6, TNF-α and IL-1β, whereas the highest contributors to positive enrichment were EGF, PDGF-BB and FGF-2. Effusion-synovitis volume decreased (mean [95%CI]) one year after HTO (-2811.58 [-5094.40, -528.76mm3]). Effusion-synovitis volume was moderately correlated (r [95% CI]) with decreased MMP-1 (0.44 [0.05; 0.71]), IL-7 (0.41 [0.00; 0.69]) and IL-1β (0.59 [0.25; 0.80]) and increased MIP-1β (0.47 [0.10; 0.73]). Medial tibiofemoral articular cartilage T2 relaxation time decreased (mean [95% CI]) one year after HTO (-0.33 [-2.69; 2.05]ms). Decreased T2 relaxation time was moderately correlated to decreased Flt-3L (0.61 [0.28; 0.81]), IL-10 (0.47 [0.09; 0.73]), IP-10 (0.42; 0.03–0.70) and increased MMP-9 (-0.41 [-0.7; -0.03]) and IL-18 (-0.48 [-0.73; -0.10]). Decreased aberrant knee mechanical loading in patients with OA is associated with decreased biological and imaging measures of inflammation (measured in synovial fluid and on MRI) and increased anabolic processes. These exploratory findings suggest that improvement in knee loading can produce long-term (one year) improvement in joint physiology.

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胫骨高位截骨术后骨关节炎滑液和磁共振成像指标的变化与关联

骨关节炎（OA）的机制生物学机制尚不清楚。我们的目标是探索1）从高胫骨截骨术（HTO）手术前到术后一年期间，使用滑液生物标志物大样本分析膝关节生理学的变化；2）滑液生物标志物的变化与膝关节积液-滑膜炎和关节软骨组成的 MRI 测量变化之间的关联。26 名有症状的膝关节 OA 和膝关节外翻患者在接受内侧开放楔形 HTO 手术前和手术后一年接受了滑液抽吸和 3 T MRI 检查。滑液中的细胞因子和生长因子水平通过多重检测法进行测量。使用基因组富集分析（GSEA）对数据蛋白质集进行本体和通路富集评估，并使用线性混合效应模型进行分析。通过手动分割对磁共振成像的渗出-滑膜炎和T2软骨弛豫时间进行分析。生物标记物浓度的变化与核磁共振成像渗出-滑膜炎体积和关节软骨T2弛豫时间的变化相关。HTO 一年后，发现 Toll 样受体和 TNF-α 信号的富集程度降低。导致这种减少的主要因素包括IL-6、TNF-α和IL-1β，而导致正富集的最大因素是EGF、PDGF-BB和FGF-2。HTO 一年后，渗出-滑膜炎体积减少（平均值 [95%CI]）（-2811.58 [-5094.40, -528.76mm3]）。渗出-滑膜炎体积与 MMP-1 (0.44 [0.05; 0.71])、IL-7 (0.41 [0.00; 0.69])和 IL-1β (0.59 [0.25; 0.80])的减少以及 MIP-1β (0.47 [0.10; 0.73])的增加呈中度相关（r [95%CI] ）。HTO 一年后，胫骨内侧关节软骨 T2 松弛时间缩短（平均值 [95% CI]）（-0.33 [-2.69; 2.05]ms）。T2 松弛时间的减少与 Flt-3L (0.61 [0.28; 0.81])、IL-10 (0.47 [0.09; 0.73])、IP-10 (0.42; 0.03-0.70) 的减少以及 MMP-9 (-0.41 [-0.7; -0.03])和 IL-18 (-0.48 [-0.73; -0.10])的增加呈中度相关。OA患者膝关节异常机械负荷的减少与炎症的生物学和影像学测量指标（滑膜液和核磁共振成像测量）的减少以及合成代谢过程的增加有关。这些探索性研究结果表明，膝关节负荷的改善可使关节生理学得到长期（一年）的改善。

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来源期刊

Arthritis Research & Therapy RHEUMATOLOGY-

CiteScore

8.60

自引率

2.00%

发文量

261

审稿时长

14 weeks

期刊介绍： Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.