Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Lingyuan West Road, NO. 56, Guangzhou, Guangdong, China.
Department of Stomatology, The Third Affiliated Hospital, Sun Yat-Sen University, Tianhe Road, NO. 600, Guangzhou, Guangdong, China.
Inflammation. 2021 Feb;44(1):80-90. doi: 10.1007/s10753-020-01310-0.
Local joint inflammation plays an important role in the pathogenesis of temporomandibular joint (TMJ) osteoarthrosis (TMJOA). Yohimbine, an alpha-2 adrenergic receptor antagonist, possesses anti-inflammatory properties; however, the ability of Yohimbine to protect against TMJOA-associated chondrocyte inflammation remains unclear. We conducted in vitro and in vivo analyses to investigate whether Yohimbine could ameliorate TMJOA-induced chondrocyte inflammation and to elucidate the mechanisms involved. Chondrocytes of TMJOA mice were stimulated with interleukin (IL)-1β or noradrenaline (NE), and the resulting production of inflammation-related factors was evaluated in the presence or absence of Yohimbine. Furthermore, two TMJOA mouse models were treated with Yohimbine and the therapeutic effect was quantified. NE (10 M) triggered inflammatory cytokine secretion by TMJ chondrocytes, and Yohimbine suppressed IL-1β- or NE-induced IL-6 upregulation in TMJ chondrocytes with the nuclear factor (NF)-κB pathway inhibition. Yohimbine also ameliorated cartilage destruction in the TMJOA models. Interestingly, αmpT, a tyrosine hydroxylase inhibitor, reversed the effects of Yohimbine by activating the NF-κB pathway. Collectively, these findings show that Yohimbine ameliorated TMJ chondrocyte inflammation and the suppression of NF-κB pathway contributes to this effect.
局部关节炎症在颞下颌关节（TMJ）骨关节炎（TMJOA）的发病机制中起重要作用。育亨宾是一种α2肾上腺素能受体拮抗剂，具有抗炎特性；然而，育亨宾是否能保护 TMJOA 相关的软骨细胞炎症尚不清楚。我们进行了体外和体内分析，以研究育亨宾是否可以改善 TMJOA 诱导的软骨细胞炎症，并阐明相关机制。用白细胞介素（IL）-1β或去甲肾上腺素（NE）刺激 TMJOA 小鼠的软骨细胞，并在存在或不存在育亨宾的情况下评估产生的炎症相关因子。此外，用育亨宾治疗两种 TMJOA 小鼠模型，并对治疗效果进行量化。NE（10μM）触发 TMJ 软骨细胞的炎症细胞因子分泌，育亨宾通过核因子（NF）-κB 途径抑制抑制 IL-1β或 NE 诱导的 IL-6 上调。育亨宾还改善了 TMJOA 模型中的软骨破坏。有趣的是，酪氨酸羟化酶抑制剂αmpT 通过激活 NF-κB 通路逆转了育亨宾的作用。总之，这些发现表明育亨宾改善了 TMJ 软骨细胞炎症，抑制 NF-κB 途径有助于这种作用。
