Current Stem Cell Research & Therapy - Volume 13, Issue 2, 2018

Background: Development is an epigenetic regulation dependent event. As one pretranscriptional regulator, bivalent histone modifications were observed to be involved in development recently. It is believed that histone methylation potentially takes charge of cell fate determination and differentiation. The synchronous existence of functionally opposite histone marks at transcript start sequence (TSS) is defined as “Bivalency”, which mainly mark development related genes. H3K4me3 and H3K27me3, the prominent histone methylations of bivalency, are implicated in transcriptional activation and transcriptional repression respectively. The delicate balance between H3K4me3 and H3K27me3 produces diverse chromatin architectures, resulting in different transcription states of downstream genes: “poised”, “activated” or “repressed”. Objective: In order to explore the developmental role of bivalent histone modification and the underlying mechanism, we did systematic review and rigorous assessment about relative literatures. Result: Bivalent histone modifications are considered to set up genes for activation during lineage commitment by H3K4me3 and repress lineage control genes to maintain pluripotency by H3K27me3. Summarily, bivalency in stem cells keeps stemness via poising differentiation relevant genes. After receiving developmental signals, the balance between “gene activation” and “gene repression” is broken, which turns genes transcription state from “poised” effect to switch on or switch off effect, thus initiates irreversible and spontaneous differentiation procedures. Conclusion: Bivalent histone modifications and the associated histone-modifying complexes safeguard proper and robust differentiation of stem cells, thus playing an essential role in development.

Background: Dentinogenesis is a long and complex process not only in tooth development, but also throughout the lifespan. Reporter mice provided us a preferred model to study the dentin formation with characteristics of high sensitivity, visualization, and reliability, which makes the long-term and intricate period of dentinogenesis much clear. With the advent of different gene reporters, genetic engineering methods, and tissue specific promoters, various reporter mice can be created to solve different problems. Objective: To understand the fundamental concepts and characteristics to use the reporter mice for dentinogenesis study. Results: This review introduced the frequently used gene–based reporters, genetic engineering technologies, dentinogenesis-related promoters and the reporter mice commonly used in the dentin study, with the purpose of obtaining a better application of reporter mice and gaining more details about dentinogenesis. Conclusion: Reporter mice is a convenient and reliable model for studying dentinogenesis.

Background: Osteoporosis is a common degenerative bone disease which is characterized with decreased bone strength and increased risk of fracture. The abnormal bone metabolism homeostasis, especially in osteoclastic function, takes a fundamental role in osteoporosis pathogenesis. In the past decade, epigenetic regulation of bone homeostasis are widely investigated and considered as a vital factor in the regulation of the differentiation and functions of osteoblasts, osteoclasts and osteocytes. The relationship between osteoporosis and epigenetic regulations has gradually become as an important issue in the mechanism study of osteoporosis. Objective: In this review, we summarize the recent progresses of epigenetic regulation mechanism in bone development and remodeling, and emphasize the epigenetic features of osteoporosis and the potent therapy application of epigenetic drugs for osteoporosis. Conclusion: DNA methylation and histone modification regulated bone development and remodeling via affecting both osteoblastogenesis and osteoclastogenesis. And the abnormal epigenetic status is relevant to bone disease such as osteoporosis and osteoarthritis. Several inhibitors of DNMTs or HDACs exhibit a potential application for osteoporosis, and the side effects of these drugs should also be considered in the future applications.

Background: Odontogenesis is fundamentally controlled by the genome. However, epigenetic factors have indispensable effects during odontogenesis. Previous studies have shown that exogenous factors, such as the environment, that cause hypomethylation and hypermethylation in DNA may lead to dental differences in monozygotic twin pairs. In addition, abnormalities in epigenetic regulation could induce disruptions in odontogenesis, thereby causing tooth malformation or agenesis. Objective: This review overviews the epigenetic mechanisms involved in odontogenesis with the aim of establishing a fundamental vision of tooth development, which might be useful in further research in odontogenesis and therapy for dental diseases. Results: We summarized articles about epigenetics in odontogenesis. Here, we present concrete epigenetic regulation mechanisms in odontogenesis that have been reported previously, following the order of microRNA, DNA methylation and histone modification. Conclusion: Epigenetic factors influence the proliferation, differentiation or apoptosis of cells that play indispensable roles during the process of odontogenesis which have the ability to exquisitely regulate the tooth number, size and shape.

Background: Tooth root development begins after the completion of tooth crown development. Both the tooth root and crown undergo a series of interactions between the epithelium and adjacent mesenchymal cells. Although many studies have evaluated tooth crown formation, little is known about the regulatory mechanisms of tooth root development. MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein expression through post-transcriptional mechanisms and participate in a broad range of biological processes, from development to tumorigenesis. The functional importance of miRNAs on the development of tooth root and periodontal tissues has been suggested in many studies. Objective: To summarize the functions of miRNAs on tooth root and periodontal tissue development. Results: MicroRNAs are important to root odontogenesis, Hertwig’s epithelial root sheath and periodontal tissue development, and have functions in stem cells from dental or periodontal tissues. Conclusion: The modulation of miRNAs in tooth root and periodontal tissue development is fine tuning.

Background: Aging is characterized by time-dependent functional decline, which results in the reduced ability to cope with physiological challenges. The aging process can be affected by genetic factors, environment factors, epigenetic factors, and several stochastic factors. Epigenetic marker alteration during aging has been widely monitored and studied recently, since these epigenetic alterations are theoretically reversible. Objectives: In this review, we will elaborate on the connection between aging and histone modifications, mainly focusing on the major modification participated in aging and its underlying mechanism. We will also summarize the latest research progress of the potential and promising treatments or strategies that aim to reverse aging through the intervention of histone modifications. Conclusion: Histone post-translational modifications play a crucial role in epigenetic alteration during aging, among which histone methylation and histone acetylation are emerging as two prominent modification methods. These modifications can serve as the therapeutic targets in the pursuit of rejuvenation.

Background: The study of epigenetic regulation has made substantial progress in recent years. The AlkB family in E. coli was identified as a type of DNA repair enzyme that removes alkyl adducts from nucleobases. Recently, nine mammalian homologs, ALKBH1-9, have been successfully identified and defined as diverse demethylases. ALKBH1, ALKBH5, ALKBH8 and ALKBH9 act as RNA demethylases, while ALKBH2-3 and ALKBH7 correct methyl and etheno adducts in DNA. Moreover, ALKBH4 focuses primarily on actin. Disorders of AlkB family level in mammals induce many types of diseases. Objectives: In this review, we will elaborate on the structure and biological function of the members of the AlkB family. We will also focus on the latest progress of the research on the mammalian AlkB family, particularly on new breakthroughs, and present the relevant disorders or diseases induced by an abnormal level of the AlkB family. Conclusion: The AlkB family plays a crucial role in embryogenesis and differentiation. The aberrant level of the AlkB family leads to many types of diseases. The members of the AlkB family may serve as potential cancer markers and possible therapeutic targets in the future.

Background: Periodontitis is a multifactorial infectious disease that affects a large population worldwide. Oral microorganisms and susceptible host have been proposed to be the prerequisite for the development of periodontitis. Recently, the involvement of epigenetic modifications in the development of periodontitis has been suggested. Objectives: This review aims to detail recent discoveries involving the epigenetic alterations in periodontitis, and discuss the possible epigenetic mechanisms contributing to the expression of periodontitis- related genes. Conclusions: The expression of inflammatory cytokines during periodontitis is regulated at epigenetic level by mechanisms such as DNA methylation, histone modification and miRNAs. In addition, periodontal pathogens and their virulence factors could induce epigenetic alterations of periodontal tissues, and thus affect the progression and prognosis of periodontitis. The involvement of epigenetic modifications during periodontitis not only advances our knowledge on the pathogenesis of periodontitis, but may also lead to the identification of potential therapeutic targets of this oral disease.

Background: Tooth development relies on interactions between epithelial and mesenchymal tissues, which are controlled by sophisticated networks of conserved signaling. The signaling networks regulating odontogenesis have been well characterized, but the epigenetic mechanisms underlying remain to be elucidated. Objective: In this review, we describe current researches regarding the control of various genes expression by DNA methylation during odontogenesis, summarize genomic mapping of DNA methylation in various stages of tooth formation and diverse dental tissues by high-throughput approaches, and highlight the roles of DNA methylation in odontogenesis. Results: Researches on mammals have revealed that the genomic methylation, which occurs on cytosine residues, regulates certain genes transcription. Consequently, DNA methylation plays a crucial role in spatiotemporal organization of signaling pathways, and is essential for organogenesis. Recently, mounting evidence proves that methylation of genomes contributes to the spatiotemporal gene dynamics during odontogenesis. With emerging new technologies of mapping cytosine modifications in global genome, investigators are seeking an overall view of DNA methylome dynamics that characterize genetic information to manifest across incredibly varied tooth development stages, dental tissues, and developmental dental defects.