Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Arthritis Rheumatol. 2023 Jun;75(6):950-960. doi: 10.1002/art.42424. Epub 2023 Mar 9.
This study aimed to determine whether alignment correction by high tibial osteotomy (HTO) can change the biologic intraarticular microenvironment of osteoarthritic (OA) knees.
Synovial tissue (ST) and fluid (SF) were collected from the affected knees of 31 OA patients during initial HTO and plate removal surgeries. Changes in gene expression in ST were investigated by microarray and real-time polymerase chain reaction (PCR). ST specimens were also evaluated histologically using synovitis scores and immunofluorescence staining to determine macrophage polarity. Cytokines and chemokines in SF were analyzed by enzyme-linked immunosorbent assays. The mechanism of macrophage polarization was investigated in human peripheral blood mononuclear cell-derived macrophages and fibroblast-like synoviocytes (FLS) stimulated with cartilage fragments. We also evaluated Spearman correlations between Knee Injury and Osteoarthritis Outcome scores (KOOS) and macrophage-related gene expression.
The microarray results indicated down-regulated inflammatory genes and pathways. Real-time PCR determined that genes expressing proinflammatory IL1B and IL6 were down-regulated and M2 macrophage-related IL1RA, IL10, CCL18, and CD206 were up-regulated. Histologic findings revealed attenuated synovitis scores and a shift from M1 to M2 macrophages. Interleukin-1β (IL-1β) concentrations in SF decreased after HTO. Cartilage fragments were responsible for M1 macrophage polarization and proinflammatory gene and protein expression in macrophages, whereas cartilage fragments up-regulated only IL-6 protein in FLS. Postoperative KOOS positively correlated with the expression of the M2-related genes CCL18 and CD206.
Correction of lower limb alignment with HTO attenuated synovial inflammation and changed macrophage polarization from M1 to M2, suggesting an improved intraarticular environment in knee OA.
本研究旨在确定胫骨高位截骨术（HTO）的对线校正是否可以改变骨关节炎（OA）膝关节的关节内生物学微环境。
在初次 HTO 和钢板取出手术期间，从 31 例 OA 患者的患病膝关节中采集滑膜组织（ST）和滑液（SF）。通过微阵列和实时聚合酶链反应（PCR）研究 ST 中的基因表达变化。还通过滑膜炎评分和免疫荧光染色评估 ST 标本，以确定巨噬细胞极性。通过酶联免疫吸附测定法分析 SF 中的细胞因子和趋化因子。通过用软骨碎片刺激人外周血单核细胞来源的巨噬细胞和成纤维样滑膜细胞（FLS）来研究巨噬细胞极化的机制。我们还评估了膝关节损伤和骨关节炎结果评分（KOOS）与巨噬细胞相关基因表达之间的 Spearman 相关性。
微阵列结果表明炎症基因和途径下调。实时 PCR 确定表达促炎细胞因子 IL1B 和 IL6 的基因下调，而 M2 巨噬细胞相关细胞因子 IL1RA、IL10、CCL18 和 CD206 上调。组织学发现滑膜炎评分降低，M1 向 M2 巨噬细胞转变。HTO 后 SF 中的白细胞介素 1β（IL-1β）浓度降低。软骨碎片负责 M1 巨噬细胞极化和巨噬细胞中的促炎基因和蛋白表达，而软骨碎片仅在上皮样滑膜细胞中上调 IL-6 蛋白。术后 KOOS 与 M2 相关基因 CCL18 和 CD206 的表达呈正相关。
HTO 矫正下肢对线可减轻滑膜炎症，并使巨噬细胞从 M1 向 M2 极化，这表明膝骨关节炎的关节内环境得到改善。
