Melatonin ameliorates inflammation-induced developmental defects of enamel by upregulating regulator of G protein signaling 2

Mengning Bi; Yucong Zhou; Xuejiao Yang; Yangyang Li; Qianhui Ren; Jing Pan; Xuanyu Wang; Yueying Wang; Fang Ji

Journal of Dental Sciences (Oct 2024)

Melatonin ameliorates inflammation-induced developmental defects of enamel by upregulating regulator of G protein signaling 2

Mengning Bi,
Yucong Zhou,
Xuejiao Yang,
Yangyang Li,
Qianhui Ren,
Jing Pan,
Xuanyu Wang,
Yueying Wang,
Fang Ji

Affiliations

Mengning Bi: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Yucong Zhou: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Xuejiao Yang: Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yangyang Li: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Qianhui Ren: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China; South China Center of Craniofacial Stem Cell Research Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology Sun Yat-Sen University, Guangzhou, China
Jing Pan: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Xuanyu Wang: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Yueying Wang: Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author. Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639 Zhizaoju Road, Shanghai 200011, China.
Fang Ji: Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China; Corresponding author. Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin second Road, Shanghai 200025, China.

Journal volume & issue: Vol. 19, no. 4
pp. 2355 – 2366

Abstract

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Background/purpose: Developmental defects of enamel (DDE) is a dental disease with a high prevalence and no effective means of prevention. One of the major causes of DDE is infection, but the pathogenesis is still unclear. Melatonin is known for its anti-inflammatory and mineralization-promoting activities. However, the effects of melatonin on inflammation-induced DDE remain unknown. Here, we investigated the pathogenesis and potential therapeutic targets of inflammation-induced DDE. Materials and methods: First, the effect of lipopolysaccharide-induced inflammation in pregnant mice on the enamel mineralization of the offspring was detected by 3D X-ray microscope analysis, immunohistochemical assays, and quantitative real-time polymerase chain reaction (qRT-PCR). Then, the ameloblastic differentiation ability of ameloblast lineage cells (ALCs) in macrophage conditioned medium (CM) was detected. Subsequently, ameloblastic mineralization after melatonin administration was studied both in vivo and in vitro. The underlying mechanism of melatonin was investigated by RNA sequencing and small interfering RNA transfection. Results: Enamel mineralization was decreased in the inflammatory environment both in vivo and in vitro. Furthermore, melatonin treatment ameliorated these defects. RNA sequencing analysis revealed that regulator of G protein signaling 2 (Rgs2) was downregulated in the inflammation group, whereas it was upregulated after the addition of melatonin. Further studies showed that Rgs2 knockdown resulted in decreased ameloblastic mineralization in ALCs. After Rgs2 knockdown of ALCs in M1-CM with melatonin, the effect of melatonin-mediated attenuation of DDE was greatly reduced. Conclusion: Our results demonstrate that melatonin ameliorates inflammation-induced DDE by upregulating RGS2, suggesting that RGS2 is a potential therapeutic target for inflammation-induced DDE.

Published in Journal of Dental Sciences

ISSN: 1991-7902 (Print)
Publisher: Elsevier
Country of publisher: Taiwan, Province of China
LCC subjects: Medicine: Dentistry
Website: http://www.journals.elsevier.com/journal-of-dental-sciences/

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