Increase in Tryptase and Its Role in the Synovial Membrane of Overweight and Obese Patients with Osteoarthritis of the Knee
Increase in Tryptase and Its Role in the Synovial Membrane of Overweight and Obese Patients with Osteoarthritis of the Knee
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DOI：
10.2147/dmso.s253147
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Takaso, Masashi
中科院分区：
文献类型：
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作者：
Takata, Ken;Uchida, Kentaro;Takaso, Masashi
目的：肥胖是骨关节炎 (OA) 危险因素的证据机制尚不清楚。我们之前报道肥胖患者骨关节炎滑膜（SM）中肥大细胞（MC）标记物表达增加。我们假设 MC 产生的一种酶（β-类胰蛋白酶）可能在肥胖膝关节 OA 患者的 SM 中增加，并导致滑膜炎症。本研究调查了肥胖膝骨关节炎患者 SM 中 β 类胰蛋白酶编码基因 TPSB2 的表达，以及滑膜细胞中 β 类胰蛋白酶介导的 IL-1 β 调节。 患者和方法：共有 216 名放射学诊断为膝骨关节炎的患者根据世界卫生组织的体重指数分类进行分组：正常体重（NW；= 30 kg/m(2)）。采用定量聚合酶链反应检测三组 SM 中 TPSB2 的表达。我们还检测了从滑膜组织新鲜分离的富含 MC（CD3-CD14-CD19-CD90-）和缺乏 MC（CD3+、CD14+、CD19+ 或 CD90+）级分中的 TPSB2 和 IL1B 表达。此外，在培养的 CD14 阳性（富含巨噬细胞的部分）和 CD14 阴性（富含成纤维细胞的部分）细胞中研究了 β-类胰蛋白酶对 IL1B 表达的影响。 结果：与 NW 组相比，OW 和 OB 组中 TPSB2 表达显着升高。富含 MC 的部分比缺乏 MC 的部分具有显着更高的 TPSB2、CD117 和 CD203c 水平。重组人 β-类胰蛋白酶刺激滑膜成纤维细胞和巨噬细胞部分中的 IL1B 表达。结论：患有膝 OA 的肥胖患者在 SM 中显示出升高的 TPSB2 表达。类胰蛋白酶可能在肥胖 OA 患者的滑膜炎症中发挥作用。
Purpose: The mechanisms governing evidence that obesity is a risk factor for osteoarthritis (OA) are not well understood. We previously reported an increase in mast cell (MC) marker expression in the osteoarthritic synovial membrane (SM) of patients with obesity. We hypothesized that an enzyme produced by MC, beta-tryptase, may be increased in the SM of obese patients with knee OA and contribute to synovial inflammation. This study investigated the expression of the beta-tryptase encoding gene, TPSB2, in the SM of obese patients with knee OA and beta-tryptase-mediated regulation of IL-1 beta in synovial cells.Patients and Methods: A total of 216 patients radiographically diagnosed with knee OA were grouped according to the World Health Organization's body mass index classifications: normal weight (NW; = 30 kg/m(2)). Quantitative polymerase chain reaction was conducted to examine TPSB2 expression in the SM among the three groups. We also examined TPSB2 and IL1B expression in MC-rich (CD3-CD14-CD19-CD90-) and MC-poor (CD3+, CD14+, CD19+, or CD90+) fractions freshly isolated from synovial tissue. Further, the effect of beta-tryptase on IL1B expression was investigated in cultured CD14-positive (macrophage-rich fraction) and CD14-negative (fibroblast-rich fraction) cells.Results: There was significantly elevated TPSB2 expression in the OW and OB groups compared to the NW group. The MC-rich fraction had significantly higher levels of TPSB2, CD117 and CD203c than the MC-poor fraction. Recombinant human beta-tryptase stimulated IL1B expression in both the synovial fibroblast and macrophage fractions.Conclusion: Obese patients with knee OA showed elevated TPSB2 expression in the SM. Tryptase may play a role in synovial inflammation in obese patients with OA.