Takata Ken, Uchida Kentaro, Mukai Manabu, Takano Shotaro, Aikawa Jun, Iwase Dai, Sekiguchi Hiroyuki, Miyagi Masayuki, Inoue Gen, Takaso Masashi
Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
Shonan University of Medical Sciences Research Institute, Chigasaki City, Kanagawa 253-0083, Japan.
Diabetes Metab Syndr Obes. 2020 May 5;13:1491-1497. doi: 10.2147/DMSO.S253147. eCollection 2020.
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, β-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 β-tryptase encoding gene, , in the SM of obese patients with knee OA and β-tryptase-mediated regulation of IL-1β in synovial cells.
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; <25 kg/m), overweight (OW; 25-29.99 kg/m) and obese (OB; ≥30 kg/m). Quantitative polymerase chain reaction was conducted to examine expression in the SM among the three groups. We also examined and 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 β-tryptase on expression was investigated in cultured CD14-positive (macrophage-rich fraction) and CD14-negative (fibroblast-rich fraction) cells.
There was significantly elevated expression in the OW and OB groups compared to the NW group. The MC-rich fraction had significantly higher levels of and than the MC-poor fraction. Recombinant human β-tryptase stimulated expression in both the synovial fibroblast and macrophage fractions.
Obese patients with knee OA showed elevated expression in the SM. Tryptase may play a role in synovial inflammation in obese patients with OA.
肥胖是骨关节炎（OA）危险因素的相关机制尚未完全明确。我们之前报道过肥胖患者骨关节炎滑膜（SM）中肥大细胞（MC）标志物表达增加。我们推测MC产生的一种酶，β-色氨酸酶，可能在肥胖膝骨关节炎患者的滑膜中增加，并导致滑膜炎症。本研究调查了肥胖膝骨关节炎患者滑膜中β-色氨酸酶编码基因的表达，以及β-色氨酸酶对滑膜细胞中白细胞介素-1β的调节作用。
根据世界卫生组织的体重指数分类，将216例经影像学诊断为膝骨关节炎的患者分为：正常体重（NW；<25kg/m）、超重（OW；25 - 29.99kg/m）和肥胖（OB；≥30kg/m）。采用定量聚合酶链反应检测三组滑膜中该基因的表达。我们还检测了从滑膜组织新鲜分离的富含MC（CD3 - CD14 - CD19 - CD90 -）和MC缺乏（CD3 +、CD14 +、CD19 +或CD90 +）部分中的该基因和另一基因的表达。此外，在培养的CD14阳性（富含巨噬细胞部分）和CD14阴性（富含成纤维细胞部分）细胞中研究了β-色氨酸酶对该基因表达的影响。
与NW组相比，OW组和OB组该基因表达显著升高。富含MC的部分中该基因和另一基因的水平显著高于MC缺乏的部分。重组人β-色氨酸酶刺激滑膜成纤维细胞和巨噬细胞部分中的该基因表达。
肥胖膝骨关节炎患者滑膜中该基因表达升高。色氨酸酶可能在肥胖骨关节炎患者的滑膜炎症中起作用。
