Liu Gufeng, Sun Quan, Wu Xiaoyi, Liu Ying, Chen Yang, Cao Zhengguo, Hu Yanhe, Xia Haibin
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Department of Periodontology, Hospital and School of Stomatology, Wuhan University, Wuhan, China.
In Vitro Cell Dev Biol Anim. 2023 Jan;59(1):76-84. doi: 10.1007/s11626-023-00748-4. Epub 2023 Feb 15.
Circadian clock genes are present in the ameloblasts, odontoblasts, and dental pulp cells. The cementum plays a vital role in connecting the roots of teeth to the alveolar bone by anchoring the periodontal ligament. The present study aimed at confirming the existence of clock genes and describing the potential regulatory effects of REV-ERBα in the cementum. The tooth-periodontal ligament-alveolar bone complexes of 6-week-old mice were analyzed using immunohistochemistry. OCCM-30 cells, an immortalized cementoblast cell line, were synchronized with dexamethasone. We used RT-PCR to detect the expression of clock genes in the absence or presence of SR8278, an effective antagonist of REV-ERBα. We performed a cell counting kit-8 (CCK-8) assay to determine the effect of SR8278 on cell proliferation. RT-PCR and Western blot were used to measure the expression of mineralization-related markers in mineralization-induced OCCM-30 cells, with or without SR8278 treatment. Finally, we used Alizarin red staining, and ALP staining and activity to further verify the effect of SR8278 on mineralization of OCCM-30 cells on macro-level. In our study, clock protein expression was confirmed in the murine cementum. Clock genes were shown to oscillate continuously in OCCM-30 cells. SR8278-induced inactivation of REV-ERBα inhibited the proliferation but promoted the mineralization of OCCM-30 cells. The present study confirmed the presence of clock genes in the cementum, where they potentially participate in cell proliferation and mineralization. Our findings may inspire new research directions for periodontal regeneration via clock gene manipulation.
昼夜节律时钟基因存在于成釉细胞、成牙本质细胞和牙髓细胞中。牙骨质通过锚定牙周韧带在将牙根与牙槽骨连接方面起着至关重要的作用。本研究旨在证实时钟基因的存在,并描述REV-ERBα在牙骨质中的潜在调节作用。使用免疫组织化学分析6周龄小鼠的牙齿-牙周韧带-牙槽骨复合体。将永生化的成牙骨质细胞系OCCM-30细胞用地塞米松进行同步化处理。我们使用逆转录聚合酶链反应(RT-PCR)检测在存在或不存在REV-ERBα有效拮抗剂SR8278的情况下时钟基因的表达。我们进行细胞计数试剂盒-8(CCK-8)分析以确定SR8278对细胞增殖的影响。使用RT-PCR和蛋白质免疫印迹法测量在有或没有SR8278处理的矿化诱导的OCCM-30细胞中矿化相关标志物的表达。最后,我们使用茜素红染色、碱性磷酸酶(ALP)染色和活性在宏观水平上进一步验证SR8278对OCCM-30细胞矿化的影响。在我们的研究中,在小鼠牙骨质中证实了时钟蛋白的表达。时钟基因在OCCM-30细胞中显示出持续振荡。SR8278诱导的REV-ERBα失活抑制了OCCM-30细胞的增殖,但促进了其矿化。本研究证实了牙骨质中存在时钟基因,它们可能参与细胞增殖和矿化。我们的发现可能会激发通过时钟基因操纵进行牙周再生的新研究方向。