Crossman Jacqueline, Lai Hollis, Kulka Marianna, Jomha Nadr, Flood Patrick, El-Bialy Tarek
Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Department of Medical Microbiology & Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Tissue Eng Part C Methods. 2021 Feb;27(2):115-123. doi: 10.1089/ten.TEC.2020.0294.
Juvenile idiopathic arthritis can affect the temporomandibular joint (TMJ) can cause growth disturbances of the lower jaw (mandible). The collagen-induced arthritis (CIA) juvenile rat model may be an appropriate model for studying how juvenile arthritis affects this joint during growth. However, studies using this animal model to investigate TMJ arthritis are limited. To validate an animal model for studying TMJ arthritis in growing rats, our study aimed to investigate the changes in mandibular growth and expression of proteins and cytokines in the mandibular condyle of CIA juvenile rat TMJs. A total of 27 male Wistar rats (3 weeks old) were scanned with microcomputed tomography (MicroCT) and divided into three groups ( = 9); CIA was induced in each TMJ in the CIA group, the Saline group received saline injections (sham injections) into their TMJs, and the Healthy group remained untreated (no TMJ injections) as negative controls. After 4 weeks, our results show that mandibular growth was significantly reduced in the CIA group compared with the Saline group ( < 0.01). There was no difference in mandibular growth between the two control groups (Saline and Healthy). Inflamed synovial tissue, cartilage invaginations, and lipid accumulation were observed in the CIA TMJs. Toluidine blue staining revealed decreased proteoglycan production in the CIA cartilage. In addition, immunohistochemistry revealed that type II collagen expression decreased, interleukin-1β expression increased, and matrix metalloproteinase-13 expression increased in the CIA TMJs in comparison with the two control groups (Saline and Healthy). Immunostaining of tumor necrosis factor-α (TNF-α) was quantified and we showed that TNF-α expression was significantly greater in the CIA cartilage compared with both control groups ( < 0.05), and there was no difference in TNF-α expression between the Saline and Healthy groups. This CIA juvenile rat model of TMJ juvenile arthritis shows that CIA reduced mandibular growth and induced degenerative changes in TMJ condylar cartilage. This new information will help to understand the pathogenesis involved in CIA in juvenile rat TMJs for this animal model to be used in research investigating new therapeutics to treat TMJ juvenile arthritis. Impact statement In this study, the effects of collagen-induced arthritis (CIA) on the temporomandibular joint (TMJ) using a juvenile rat model were investigated. Our results showed that local injection of CIA in the TMJ significantly reduced mandibular growth and caused degenerative changes in condylar cartilage. This information helps to validate this animal model for studying the effect of arthritis in TMJs in growing rats. This model has the potential to be used in future studies to evaluate possible therapies for TMJ arthritis.
幼年特发性关节炎可累及颞下颌关节(TMJ),并可导致下颌骨生长紊乱。胶原诱导性关节炎(CIA)幼年大鼠模型可能是研究幼年关节炎在生长过程中如何影响该关节的合适模型。然而,利用这种动物模型研究颞下颌关节炎的研究有限。为了验证一种用于研究生长中大鼠颞下颌关节炎的动物模型,我们的研究旨在调查CIA幼年大鼠颞下颌关节下颌骨生长以及下颌髁突中蛋白质和细胞因子表达的变化。总共27只雄性Wistar大鼠(3周龄)接受了微型计算机断层扫描(MicroCT),并分为三组(每组 = 9只);CIA组的每个颞下颌关节均诱导产生CIA,生理盐水组的大鼠颞下颌关节接受生理盐水注射(假注射),健康组作为阴性对照未接受任何处理(未进行颞下颌关节注射)。4周后,我们的结果显示,与生理盐水组相比,CIA组的下颌骨生长显著降低(P < 0.01)。两个对照组(生理盐水组和健康组)之间的下颌骨生长没有差异。在CIA组的颞下颌关节中观察到滑膜组织发炎、软骨内陷和脂质积聚。甲苯胺蓝染色显示CIA组软骨中的蛋白聚糖产生减少。此外,免疫组织化学显示,与两个对照组(生理盐水组和健康组)相比,CIA组颞下颌关节中的II型胶原蛋白表达减少,白细胞介素-1β表达增加,基质金属蛋白酶-13表达增加。对肿瘤坏死因子-α(TNF-α)进行免疫染色定量分析,结果显示,与两个对照组相比,CIA组软骨中的TNF-α表达显著更高(P < 0.05),生理盐水组和健康组之间的TNF-α表达没有差异。这种CIA幼年大鼠颞下颌关节炎模型表明,CIA会降低下颌骨生长,并诱导颞下颌关节髁突软骨发生退行性变化。这些新信息将有助于理解幼年大鼠颞下颌关节中CIA的发病机制,以便将这种动物模型用于研究治疗颞下颌幼年关节炎的新疗法。影响声明 在本研究中,我们使用幼年大鼠模型研究了胶原诱导性关节炎(CIA)对颞下颌关节(TMJ)的影响。我们的结果表明,在颞下颌关节局部注射CIA可显著降低下颌骨生长,并导致髁突软骨发生退行性变化。这些信息有助于验证这种动物模型用于研究生长中大鼠颞下颌关节关节炎的作用。该模型有可能用于未来的研究,以评估颞下颌关节炎的可能治疗方法。