Abstract
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.