Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular cartilage degeneration and chronic pain. Research into OA animal models suggests that elevated NGF levels in the synovium contribute to pain and central sensitization (CS). However, it is unclear whether synovial NGF contributes to CS in patients with OA. We investigated the association between synovial NGF expression and clinical assessments of pain and CS in hip OA (hOA) patients. We also aimed to identify which cells in the synovium of hOA patients express NGF. Sixty-six patients who received total hip replacement and a diagnosis of hOA were enrolled. We measured NGF mRNA expression in synovial samples obtained from 50 patients using qPCR and analyzed the correlation of NGF expression with the CS inventory (CSI) score and Japanese Orthopaedic Association (JOA) score, a clinical scoring system for OA. To identify the synovial cells expressing NGF, we analyzed NGF mRNA expression in CD14+ and CD14- cells, which represent macrophage-rich and fibroblast-rich fractions, respectively, extracted from 8 patients. To further identify which macrophage subtypes express NGF, we examined NGF mRNA expression in CD14^high and CD14^low cells sorted from 8 patients. Synovial NGF mRNA expression was negatively correlated with JOA score but positively correlated with CSI score (JOA pain, , ; CSI score, , ). Significantly greater levels of NGF were observed in CD14- cells compared to CD14+ cells () and in CD14^high cells compared to CD14^low cells (). In conclusion, synovial NGF expression is correlated with the degree of pain and CS in hOA patients. NGF is predominantly expressed in synovial fibroblasts. Further, CD14^high synovial macrophages expressed higher levels of NGF. Our results may provide a novel NGF-targeted therapeutic strategy for hOA pain.

中文翻译：

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伴有疼痛和中枢敏化的髋骨关节炎患者 NGF 表达和升高

骨关节炎（OA）是一种慢性退行性肌肉骨骼疾病，会导致关节软骨退化和慢性疼痛。对 OA 动物模型的研究表明，滑膜中 NGF 水平升高会导致疼痛和中枢敏化 (CS)。然而，目前尚不清楚滑膜 NGF 是否有助于 OA 患者的 CS。我们调查了髋关节 OA (hOA) 患者滑膜 NGF 表达与疼痛和 CS 临床评估之间的关联。我们还旨在确定 hOA 患者滑膜中哪些细胞表达 NGF。入组了 66 名接受全髋关节置换术并诊断为 hOA 的患者。我们使用 qPCR 测量了从 50 名患者获得的滑膜样本中NGF mRNA 的表达，并分析了NGF的相关性用 CS 库存 (CSI) 评分和日本骨科协会 (JOA) 评分表达，这是一种 OA 的临床评分系统。为了鉴定表达 NGF 的滑膜细胞，我们分析了 CD14+ 和 CD14- 细胞中NGF mRNA 的表达，它们分别代表从 8 名患者中提取的富含巨噬细胞和富含成纤维细胞的部分。为了进一步确定哪些巨噬细胞亚型表达 NGF，我们检查了从 8 名患者中分选的 CD14^高和 CD14^低细胞中NGF mRNA 的表达。滑膜NGF mRNA 表达与 JOA 评分呈负相关，但与 CSI 评分（JOA 疼痛、, ; CSI分数，, ）。与 CD14+ 细胞相比，在 CD14- 细胞中观察到显着更高水平的NGF （)和 CD14^高细胞与 CD14^低细胞 (）。总之，滑膜 NGF 表达与 hOA 患者的疼痛程度和 CS 相关。NGF主要在滑膜成纤维细胞中表达。此外，CD14^高的滑膜巨噬细胞表达更高水平的 NGF。我们的结果可能为 hOA 疼痛提供一种新的 NGF 靶向治疗策略。