de Sousa Luane Macêdo, de Figueiredo Costa Ana Carolina, Pereira Anamaria Falcão, da Silva Martins Conceição, de Oliveira Filho Osias Vieira, Goes Paula, Vale Mariana Lima, Gondim Delane Viana
Postgraduate Program in Morphofunctional Sciences, Faculty of Medicine, Federal University of Ceará, Brazil.
Postgraduate Program in Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Brazil.
Bone Rep. 2023 Jan 16;18:101649. doi: 10.1016/j.bonr.2022.101649. eCollection 2023 Jun.
The canonical Wnt pathway participates in inflammatory diseases and it is involved in neuropathic pain. This study evaluated the immunoexpression of the canonical Wnt signaling pathway in the articular cartilage of the temporomandibular joint (TMJ) and along the nociceptive trigeminal pathway in arthritic rats. For this, male Wistar rats were divided into Control (C) and Arthritic (RA) groups. Arthritis induction was performed through subcutaneous injection of methylated bovine serum albumin (mBSA) and complete Freund Adjuvant (CFA)/ Incomplete Freund Adjuvant (IFA) on the first 14 days (once a week), followed by 3 weekly intra-articular injections of mBSA (10 μl/joint; left TMJ). The following parameters were evaluated: nociceptive threshold, inflammatory infiltrate, type I and III collagen birefringence, immunohistochemistry for IL-1β, TNF-α, IL-6, Wnt10b, β-catenin, cyclin-D1 in articular cartilage, c-Myc in synovial membrane, and immunofluorescence analysis for c-Fos, Wnt-10b and β-catenin in the trigeminal ganglion and the trigeminal subnucleus caudalis. The RA group showed intense articular cartilage damage with proliferation of type III collagen, increased immunoexpression of proinflammatory cytokines and Wnt-10b, β-catenin and cyclin-D1 in the articular cartilage and c-Myc in the synovial membrane. In the RA group, a reduction in the nociceptive threshold was observed, followed by a significant increase in the expression of Wnt-10b in neurons and β-catenin in satellite cells of the trigeminal ganglion. c-Fos immunoexpression was observed in neurons, peripherally and centrally, in arthritic rats. Our data demonstrated that TMJ arthritis in rats causes articular cartilage damage and nociceptive behavior, with increased immunoexpression of canonical Wnt pathway in the articular cartilage and trigeminal ganglion.
经典Wnt信号通路参与炎症性疾病，并与神经性疼痛有关。本研究评估了经典Wnt信号通路在关节炎大鼠颞下颌关节（TMJ）软骨及伤害性三叉神经通路中的免疫表达。为此，将雄性Wistar大鼠分为对照组（C）和关节炎组（RA）。在最初14天（每周一次）通过皮下注射甲基化牛血清白蛋白（mBSA）和完全弗氏佐剂（CFA）/不完全弗氏佐剂（IFA）诱导关节炎，随后每周3次向关节内注射mBSA（10μl/关节；左侧TMJ）。评估了以下参数：伤害性阈值、炎症浸润、I型和III型胶原双折射、关节软骨中IL-1β、TNF-α、IL-6、Wnt10b、β-连环蛋白、细胞周期蛋白D1的免疫组化，滑膜中c-Myc的免疫组化，以及三叉神经节和三叉神经尾侧亚核中c-Fos、Wnt-10b和β-连环蛋白的免疫荧光分析。RA组显示出严重的关节软骨损伤，伴有III型胶原增生，关节软骨中促炎细胞因子、Wnt-10b、β-连环蛋白和细胞周期蛋白D1以及滑膜中c-Myc的免疫表达增加。在RA组中，观察到伤害性阈值降低，随后三叉神经节神经元中Wnt-10b和卫星细胞中β-连环蛋白的表达显著增加。在关节炎大鼠的外周和中枢神经元中观察到c-Fos免疫表达。我们的数据表明，大鼠TMJ关节炎会导致关节软骨损伤和伤害性行为，关节软骨和三叉神经节中经典Wnt信号通路的免疫表达增加。
