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.

中文翻译：

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胫骨高位截骨术后骨关节炎滑液与磁共振成像标志物的变化及关联


骨关节炎 （OA） 的机械生物学机制尚不清楚。我们的目标是探索： 1） 使用大量滑液生物标志物从胫骨高位截骨术 （HTO） 手术前到手术后一年的膝关节生理学变化，以及 2） 滑液生物标志物的变化与膝关节积液-滑膜炎和关节软骨成分的 MRI 测量值变化的关联。26 例有症状的膝关节 OA 和内翻力线患者在内侧开口楔形 TTO 之前和之后 1 年接受了滑液穿刺和 3 T MRI。用多重测定法测量滑液中的细胞因子和生长因子水平。使用数据蛋白集和基因集富集分析 （GSEA） 评估本体和通路富集，并使用线性混合效应模型进行分析。使用手动分割分析 MRI 的积液滑膜炎和 T2 软骨松弛时间。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。HTO 后 1 年检测到 Toll 样受体和 TNF-α 信号的富集减少。这种减少的主要贡献者包括 IL-6 、 TNF-α 和 IL-1β，而阳性富集的最大贡献者是 EGF 、 PDGF-BB 和 FGF-2。HTO 后 1 年积液滑膜炎体积减少 （平均值 [95%CI]） （-2811.58 [-5094.40， -528.76mm3]）。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]） 降低以及 MIP-1β 升高 （0.47 [0.10; 0.73]） 呈中等相关性 （r [95% CI]）。HTO 后 1 年，胫股内侧关节软骨 T2 弛豫时间减少 （平均值 [95% CI]） （-0.33 [-2.69; 2.05] ms）。 T2 弛豫时间缩短与 Flt-3L （0.61 [0.28; 0.81]）、IL-10 （0.47 [0.09; 0.73]）、IP-10 （0.42; 0.03–0.70） 和 MMP-9 （-0.41 [-0.7; -0.03]） 和 IL-18 （-0.48 [-0.73; -0.10]） 升高呈中等相关性。OA 患者异常膝关节机械负荷减少与炎症的生物学和影像学测量减少（在滑液和 MRI 中测量）和合成代谢过程增加有关。这些探索性发现表明，膝关节负荷的改善可以产生关节生理学的长期（一年）改善。