We have previously reported that the interleukin-23 p19 subunit (IL-23p19) is required for experimental inflammatory arthritic pain-like behavior and disease. Even though inflammation is often a characteristic feature of osteoarthritis (OA), IL-23 is not usually considered as a therapeutic target in OA. We began to explore the role of IL-23p19 in OA pain and disease utilizing mouse models of OA and patient samples. The role of IL-23p19 in two mouse models of OA, namely collagenase-induced OA and monosodium iodoacetate-induced OA, was investigated using gene-deficient male mice. Pain-like behavior and arthritis were assessed by relative static weight distribution and histology, respectively. In knee synovial tissues from a small cohort of human OA patients, a correlation analysis was performed between IL-23A gene expression and Oxford knee score (OKS), a validated Patient Reported Outcome Measure. We present evidence that i) IL-23p19 is required for the development of pain-like behavior and optimal disease, including cartilage damage and osteophyte formation, in two experimental OA models and ii) IL-23A gene expression in OA knee synovial tissues correlates with a lower OKS (r = −0.742, p = 0.0057). The findings support the possible targeting of IL-23 as a treatment for OA pain and disease progression.

中文翻译：

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IL-23p19 在骨关节炎疼痛和疾病中的作用


我们之前曾报道过，实验性炎症关节炎疼痛样行为和疾病需要白介素 23 p19 亚基 (IL-23p19)。尽管炎症通常是骨关节炎 (OA) 的一个特征，但 IL-23 通常不被视为 OA 的治疗靶点。我们开始利用 OA 小鼠模型和患者样本探索 IL-23p19 在 OA 疼痛和疾病中的作用。使用基因缺陷的雄性小鼠研究了 IL-23p19 在两种 OA 小鼠模型（即胶原酶诱导的 OA 和碘乙酸钠诱导的 OA）中的作用。分别通过相对静态重量分布和组织学评估疼痛样行为和关节炎。在一小群人类 OA 患者的膝关节滑膜组织中，对 IL-23A 基因表达与牛津膝关节评分 (OKS)（一项经过验证的患者报告结果测量）之间进行了相关性分析。我们提供的证据表明，i) 在两个实验性 OA 模型中，IL-23p19 对于疼痛样行为和最佳疾病（包括软骨损伤和骨赘形成）的发展是必需的，ii) OA 膝关节滑膜组织中的 IL-23A 基因表达与较低的 OKS（r = −0.742，p = 0.0057）。这些发现支持 IL-23 可能作为治疗 OA 疼痛和疾病进展的靶向药物。