Niu Chenguang, Xiao Fei, Yuan Keyong, Hu XuChen, Lin Wenzhen, Ma Rui, Zhang Xiaoling, Huang Zhengwei
Shanghai Key Laboratory of Stomatology, Department of Endodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghai, China.
Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai, China.
Front Pharmacol. 2017 Sep 12;8:626. doi: 10.3389/fphar.2017.00626. eCollection 2017.
Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysaccharide (LPS)-induced alveolar bone loss, and the associated mechanisms were elucidated. Nd effectively suppressed LPS-induced alveolar bone loss and reduced osteoclast (OC) numbers Nd suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated OC differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Further investigation revealed that Nd suppressed osteoclastogenesis by suppressing the ERK and JNK signaling pathways, scavenging reactive oxygen species, and suppressing the activation of PLCγ2 that consequently affects the expression and/or activity of the OC-specific transcription factors, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). In addition, Nd significantly reduced the expression of OC-specific markers in mouse bone marrow-derived pre-OCs, including , cathepsin K (), , and . Collectively, these findings suggest that Nd has beneficial effects on bone, and the suppression of OC number implies that the effect is exerted directly on osteoclastogenesis.
牙周炎是一种慢性炎症性疾病，会损害牙齿支持组织（即牙周组织）的完整性，牙周组织包括牙龈、牙周膜和牙槽骨。在本研究中，在脂多糖（LPS）诱导的牙槽骨丧失模型中测试了nardosinone（Nd）对骨的影响，并阐明了相关机制。Nd有效抑制LPS诱导的牙槽骨丧失并减少破骨细胞（OC）数量。Nd以剂量依赖性方式抑制核因子κB受体激活剂配体（RANKL）介导的OC分化、骨吸收和F-肌动蛋白环形成。进一步研究表明，Nd通过抑制ERK和JNK信号通路、清除活性氧以及抑制PLCγ2的激活来抑制破骨细胞生成，而PLCγ2的激活会影响OC特异性转录因子c-Fos和活化T细胞核因子细胞质1（NFATc1）的表达和/或活性。此外，Nd显著降低了小鼠骨髓来源的前OC中OC特异性标志物的表达，包括组织蛋白酶K、、和。总体而言，这些发现表明Nd对骨具有有益作用，而OC数量的抑制意味着该作用直接作用于破骨细胞生成。
