PER2 regulates odontoblastic differentiation of dental papilla cells in vitro via intracellular ATP content and reactive oxygen species levels.

Background: Dental papilla cells (DPCs) are one of the key stem cells for tooth development, eventually forming dentin and pulp. Previous studies have reported that PER2 is expressed in a 24-hour oscillatory pattern in DPCs in vitro. In vivo, PER2 is highly expressed in odontoblasts (which are differentiated from DPCs). However, whether PER2 modulates the odontogenic differentiation of DPCs is uncertain. This research was to identify the function of PER2 in the odontogenic differentiation of DPCs and preliminarily explore its mechanisms. Methods: We monitored the expression of PER2 in DPCs differentiated in vivo. We used PER2 overexpression and knockdown studies to assess the role of PER2 in DPC differentiation and performed intracellular ATP content and reactive oxygen species (ROS) assays to further investigate the mechanism. Results: PER2 expression was considerably elevated throughout the odontoblastic differentiation of DPCs in vivo. Overexpressing Per2 boosted levels of odontogenic differentiation markers, such as dentin sialophosphoprotein (Dspp), dentin matrix protein 1 (Dmp1), and alkaline phosphatase (Alp), and enhanced mineralized nodule formation in DPCs. Conversely, the downregulation of Per2 inhibited the differentiation of DPCs. Additionally, downregulating Per2 further affected intracellular ATP content and ROS levels during DPC differentiation. Conclusion: Overall, we demonstrated that PER2 positively regulates the odontogenic differentiation of DPCs, and the mechanism may be related to mitochondrial function as shown by intracellular ATP content and ROS levels.

Roles of LonP1 in Oral-Maxillofacial Developmental Defects and Tumors: A Novel Insight.

Recent studies have indicated a central role for LonP1 in mitochondrial function. Its physiological functions include proteolysis, acting as a molecular chaperone, binding mitochondrial DNA, and being involved in cellular respiration, cellular metabolism, and oxidative stress. Given its vital role in energy metabolism, LonP1 has been suggested to be associated with multi-system neoplasms and developmental disorders. In this study, we investigated the roles, possible mechanisms of action, and therapeutic roles of LonP1 in oral and maxillofacial tumor development. LonP1 was highly expressed in oral-maxillofacial cancers and regulated their development through a sig-naling network. LonP1 may therefore be a promising anticancer therapy target. Mutations in LONP1 have been found to be involved in the etiology of cerebral, ocular, dental, auricular, and skeletal syndrome (CODAS). Only patients carrying specific LONP1 mutations have certain dental abnormalities (delayed eruption and abnormal morphology). LonP1 is therefore a novel factor in the development of oral and maxillofacial tumors. Greater research should therefore be conducted on the diagnosis and therapy of LonP1-related diseases to further define LonP1-associated oral phenotypes and their underlying molecular mechanisms.

ROR: Nuclear Receptor for Melatonin or Not?

Whether the retinoic acid-related orphan receptor (ROR) is a nuclear receptor of melatonin remains controversial. ROR is inextricably linked to melatonin in terms of its expression, function, and mechanism of action. Additionally, studies have illustrated that melatonin functions analogous to ROR ligands, thereby modulating the transcriptional activity of ROR. However, studies supporting these interactions have since been withdrawn. Furthermore, recent crystallographic evidence does not support the view that ROR is a nuclear receptor of melatonin. Some other studies have proposed that melatonin indirectly regulates ROR activity rather than directly binding to ROR. This review aims to delve into the complex relationship of the ROR receptor with melatonin in terms of its structure, expression, function, and mechanism. Thus, we provide the latest evidence and views on direct binding as well as indirect regulation of ROR by melatonin, dissecting both viewpoints in-depth to provide a more comprehensive perspective on this issue.

Potential risk of certain cancers among patients with Periodontitis: a supplementary meta-analysis of a large-scale population.

Background: Some studies have reported biological linkages between periodontitis and esophageal cancer, prostate cancer, kidney cancer, hematological malignancy, and melanoma of the skin. This meta-analysis aimed to assess the relationship between periodontitis and the aforementioned five cancers. Methods: Eligible studies on the association between periodontitis and the aforementioned five kinds of cancers were retrieved. The statistical analysis was conducted using Stata 12.0. Results: Ten articles (more than 100,000 samples for most cancers) were included. With statistical significance, participants with periodontitis might have enhanced risks of esophageal cancer (HR = 1.79, 95% CI: 1.15-2.79), prostate cancer (HR = 1.20, 95% CI: 1.09-1.31), hematological malignancy (HR = 1.19, 95% CI: 1.09-1.29), and melanoma of skin (HR = 1.21, 95% CI: 1.03-1.42), compared with those without periodontitis. However, the evidence regarding the correlation between periodontitis and the susceptibility to kidney cancer was lacking (HR=1.30, 95% CI: 0.96-1.76). Conclusions: The present meta-analysis revealed a potential link between periodontitis and esophageal cancer, prostate cancer, hematological malignancy, and melanoma of the skin. However, multi-center studies with large sample sizes and multivariable adjustments are still needed to support the conclusion.