Department of Orthopaedic Surgery, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.
PLoS One. 2020 Jan 10;15(1):e0227596. doi: 10.1371/journal.pone.0227596. eCollection 2020.
High tibial osteotomy (HTO) is a well-established treatment for medial compartmental knee osteoarthritis. Several microRNAs (miRNAs) are involved in osteoarthritis progression and are useful as osteoarthritis-related biomarkers. In this prospective study, we investigated differentially expressed microRNAs in the synovial fluid (SF) before and after HTO in patients with medial compartmental knee osteoarthritis to identify microRNAs that can be used as prognostic biomarkers. We used miRNA-PCR arrays to screen for miRNAs in SF samples obtained preoperatively and 6 months postoperatively from 6 patients with medial compartmental knee osteoarthritis who were treated with medial open wedge HTO. Differentially expressed miRNAs identified in the profiling stage were validated by real-time quantitative PCR in 22 other patients who had also been treated with HTO. All patients radiographically corresponded to Kellgren-Lawrence grade II or III with medial compartmental osteoarthritis. These patients were clinically assessed using a visual analogue scale and Western Ontario McMaster Universities scores. Mechanical axis changes were measured on standing anteroposterior radiographs of the lower limbs assessed preoperatively and at 6 months postoperatively. Among 84 miRNAs known to be involved in the inflammatory process, 14 were expressed in all SF specimens and 3 (miR-30a-5p, miR-29a-3p, and miR-30c-5p) were differentially expressed in the profiling stage. These 3 miRNAs, as well as 4 other miRNAs (miR-378a-5p, miR-140-3p, miR-23a-3p, miR-27b-3p), are related to osteoarthritis progression. These results were validated in the SF from 22 patients. Clinical and radiological outcomes improved after HTO in all patients, and only 2 miRNAs (miR-30c-5p and miR-23a-3p) were significantly differentially expressed between preoperative and postoperative 6-month SF samples (p = 0.006 and 0.007, respectively). Of these two miRNAs, miR-30c-5p correlated with postoperative pain relief. This study provides potential prognostic miRNAs after HTO and further investigations should be considered to determine clinical implications of these miRNAs.
胫骨高位截骨术 (HTO) 是治疗内侧间室膝骨关节炎的一种成熟治疗方法。几种 microRNAs（miRNAs）参与骨关节炎的进展，可用作骨关节炎相关的生物标志物。在这项前瞻性研究中，我们研究了内侧间室膝骨关节炎患者 HTO 前后滑液 (SF) 中差异表达的 microRNAs，以确定可作为预后生物标志物的 microRNAs。我们使用 miRNA-PCR 阵列筛选术前和术后 6 个月内侧间室骨关节炎患者的 SF 样本中的 microRNAs，这些患者接受内侧开放楔形 HTO 治疗。在 22 名接受 HTO 治疗的其他患者中，通过实时定量 PCR 验证了分析阶段鉴定出的差异表达的 microRNAs。所有患者的影像学均符合内侧间室骨关节炎的 Kellgren-Lawrence II 级或 III 级。这些患者通过视觉模拟评分和西安大略和麦克马斯特大学骨关节炎指数进行临床评估。在术前和术后 6 个月的下肢站立前后位 X 线片上测量机械轴的变化。在已知参与炎症过程的 84 种 miRNA 中，有 14 种在所有 SF 标本中表达，3 种（miR-30a-5p、miR-29a-3p 和 miR-30c-5p）在分析阶段差异表达。这 3 种 miRNA 以及另外 4 种 miRNA（miR-378a-5p、miR-140-3p、miR-23a-3p、miR-27b-3p）与骨关节炎的进展有关。这些结果在 22 名患者的 SF 中得到验证。所有患者在 HTO 后临床和影像学结果均得到改善，只有 2 种 miRNA（miR-30c-5p 和 miR-23a-3p）在术前和术后 6 个月的 SF 样本中差异表达显著（p=0.006 和 0.007）。在这两种 miRNA 中，miR-30c-5p 与术后疼痛缓解相关。本研究为 HTO 后提供了潜在的预后 microRNAs，应进一步研究以确定这些 microRNAs的临床意义。
