高胫骨截骨术后滑液与骨关节炎磁共振成像标志物的变化及相关性。

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

机构信息

School of Physical Therapy, Faculty of Health Sciences, Western University, London, ON, Canada.

Bone and Joint Institute, Western University, London, ON, Canada.

出版信息

Arthritis Res Ther. 2024 Oct 10;26(1):176. doi: 10.1186/s13075-024-03409-3.

DOI:10.1186/s13075-024-03409-3

PMID:39390512

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11465750/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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, -528.76mm]). 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]).

CONCLUSIONS

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.

摘要

背景

骨关节炎（OA）的机械生物学机制尚不清楚。我们的目的是探讨：1）使用大量滑液生物标志物从高胫骨截骨（HTO）术前到术后 1 年，研究膝关节生理学的变化，2）滑液生物标志物的变化与 MRI 测量的膝关节积液-滑膜炎和关节软骨成分的变化之间的关联。

方法

26 例有症状的膝关节 OA 和内翻畸形的患者接受了滑液抽吸和 3T MRI 检查，分别在 HTO 术前和术后 1 年进行。使用多重分析测定滑液中的细胞因子和生长因子水平。使用基因集富集分析（GSEA）对数据蛋白组进行本体论和途径富集分析，并使用线性混合效应模型进行分析。使用手动分割分析 MRI 以评估积液-滑膜炎和 T2 软骨弛豫时间。生物标志物浓度的变化与 MRI 积液-滑膜炎体积和关节软骨 T2 弛豫时间的变化相关。

结果

在 HTO 术后 1 年，检测到 Toll 样受体和 TNF-α信号的富集减少。导致这种减少的主要因素包括 IL-6、TNF-α和 IL-1β，而对正富集的最高贡献者是 EGF、PDGF-BB 和 FGF-2。术后 1 年，膝关节积液-滑膜炎体积减少（平均值[95%CI]）（-2811.58[-5094.40，-528.76mm]）。膝关节积液-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]）的降低以及 MIP-1β（0.47[0.10；0.73]）的升高呈中度相关。术后 1 年，膝关节内侧胫骨股骨关节软骨 T2 弛豫时间降低（平均值[95%CI]）（-0.33[-2.69；2.05]ms）。T2 弛豫时间的降低与 Flt-3L（0.61[0.28；0.81]）、IL-10（0.47[0.09；0.73]）、IP-10（0.42；0.03-0.70）的降低和 MMP-9（-0.41[-0.7；-0.03]）和 IL-18（-0.48[-0.73；-0.10]）的升高呈中度相关。