AZD8835 inhibits osteoclastogenesis and periodontitis-induced alveolar bone loss in rats
AZD8835 inhibits osteoclastogenesis and periodontitis-induced alveolar bone loss in rats
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AZD8835 抑制大鼠破骨细胞生成和牙周炎引起的牙槽骨丢失
DOI：
10.1002/jcp.27711
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Zhang, Shanyong
中科院分区：
文献类型：
--
作者：
Wang, Yexin;Chen, Xuzhuo;Zhang, Shanyong
慢性牙周炎（CP）是最常见的口腔疾病之一，其特征是成人结缔组织和牙槽骨的丧失。AZD8835是一种新型的双磷脂酰肌醇 - 3 - 激酶（PI3K）抑制剂，目前正处于治疗乳腺癌的1期临床评估阶段。然而，AZD8835对牙齿和牙槽骨健康是否有任何影响仍不清楚。在本研究中，我们旨在探究AZD8835在体外和体内治疗慢性牙周炎的潜在作用。我们发现AZD8835能够抑制破骨细胞分化、骨吸收，并下调破骨细胞标记基因的表达，如抗酒石酸酸性磷酸酶（Trap）、组织蛋白酶K（Ctsk）、V - ATP酶d2（Atp6v0d2）和降钙素受体（Ctr）。此外，AZD8835通过抑制核因子κB受体活化因子配体（RANKL）诱导的骨髓单核细胞（BMMs）中的PI3K/蛋白激酶B（AKT）、细胞外信号调节激酶和核因子 - κB信号通路来抑制破骨细胞生成。在体内，AZD8835极大地改善了慢性牙周炎大鼠的牙槽骨（ABL）丧失情况。同时，组织学检查显示治疗组的破骨细胞更少。总之，这些结果表明AZD8835是一种有希望减少慢性牙周炎中牙槽骨丧失的药物。
Chronic periodontitis (CP) is one of the most common oral diseases, which is characterized by the loss of connective tissue and alveolar bone in adults. AZD8835, a novel dual phosphoinositide-3-kinase (PI3K) inhibitor, is currently in phase 1 clinical evaluation to treat breast cancer. However, whether AZD8835 has any effect on teeth and alveolar bone health remains unclear. In the current study, we aimed to investigate the potential effect of AZD8835 in treating CP in vitro and in vivo. We found that AZD8835 could inhibit osteoclast differentiation, bone resorption, and downregulate the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (Trap), cathepsin K (Ctsk), V-ATPase d2 (Atp6v0d2), and calcitonin receptor (Ctr). In addition, AZD8835 suppressed osteoclastogenesis by inhibiting receptor activator of nuclear factor kappa B ligand (RANKL)-induced PI3K/protein kinase B (AKT), extracellular signal-regulated kinase, and nuclear factor-B signaling in BMMs. In vivo, AZD8835 greatly ameliorated alveolar bone (ABL) loss in rats with CP. Meanwhile, histological examination showed fewer osteoclasts in the treatment group. In conclusion, these results indicated that AZD8835 is a promising agent to reduce ABL in CP.