Post Graduate Program in Morphofunctional Sciences, Department of Morphology, Federal University of Ceará, Rua Delmiro de Farias, S/N, Rodolfo Teófilo, Fortaleza, CE, CEP 60416-030, Brazil.
Post Graduate Program in Dentistry, Department of Clinical Dentistry, Federal University of Ceará, Fortaleza, CE, Brazil.
Inflamm Res. 2019 Oct;68(10):889-900. doi: 10.1007/s00011-019-01274-4. Epub 2019 Aug 1.
To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat temporomandibular joint (TMJ).
Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1β, NF-κB, RANKL, Wnt-10b, β-catenin and DKK1.
The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1β and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear β-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections.
Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.
研究经典 Wnt 和 NF-κB 信号通路在大鼠颞下颌关节(TMJ)慢性关节炎实验模型中的作用。
Wistar 大鼠于第 1-14 天(每周 1 次)接受 mBSA+CFA/IFA 致敏,随后每周 1 次接受 1、2 或 3 次 mBSA 或生理盐水 TMJ 注射。在整个实验过程中评估高敏痛阈。mBSA 注射后 24 小时,取出 TMJ 进行 TNF-α、IL-1β、NF-κB、RANKL、Wnt-10b、β-catenin 和 DKK1 的组织病理学和免疫组织化学分析。
mBSA 注射后痛阈明显降低。仅在 mBSA 加强注射后观察到炎症浸润和滑膜增厚。关节炎组滑膜中 TNF-α、IL-1β 和 Wnt-10b 的免疫标记增加。只有在接受 2 次 TMJ 加强注射的组中,核β-catenin 的免疫表达显著升高。然而,只有在接受 3 次关节内 mBSA 注射的动物中,NF-κB、RANKL 和 DKK1 的免疫表达才增加。
我们的结果表明,经典 Wnt 和 NF-κB 信号通路参与了大鼠类风湿性关节炎发展过程中 TMJ 滑膜的高敏痛觉和炎症反应。