The etiology of dental caries remains elusive because of our limited understanding of the complex oral microbiomes. The current methodologies have been limited by insufficient depth and breadth of microbial sampling, paucity of data for diseased hosts particularly at the population level, inconsistency of sampled sites and the inability to distinguish the underlying microbial factors. By cross-validating 16S rRNA gene amplicon-based and whole-genome-based deep-sequencing technologies, we report the most in-depth, comprehensive and collaborated view to date of the adult saliva microbiomes in pilot populations of 19 caries-active and 26 healthy human hosts. We found that: first, saliva microbiomes in human population were featured by a vast phylogenetic diversity yet a minimal organismal core; second, caries microbiomes were significantly more variable in community structure whereas the healthy ones were relatively conserved; third, abundance changes of certain taxa such as overabundance of Prevotella Genus distinguished caries microbiota from healthy ones, and furthermore, caries-active and normal individuals carried different arrays of Prevotella species; and finally, no ‘caries-specific’ operational taxonomic units (OTUs) were detected, yet 147 OTUs were ‘caries associated’, that is, differentially distributed yet present in both healthy and caries-active populations. These findings underscored the necessity of species- and strain-level resolution for caries prognosis, and were consistent with the ecological hypothesis where the shifts in community structure, instead of the presence or absence of particular groups of microbes, underlie the cariogenesis.

Regenerative endodontic procedures (REPs) is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis. The ultimate objective of REPs is to regenerate the pulp-dentin complex, extend the tooth longevity and restore the normal function. Scientific evidence has demonstrated the efficacy of REPs in promotion of root development through case reports, case series, cohort studies, and randomized controlled studies. However, variations in clinical protocols for REPs exist due to the empirical nature of the original protocols and rapid advancements in the research field of regenerative endodontics. The heterogeneity in protocols may cause confusion among dental practitioners, thus guidelines and considerations of REPs should be explicated. This expert consensus mainly discusses the biological foundation, the available clinical protocols and current status of REPs in treating immature teeth with pulp necrosis, as well as the main complications of this treatment, aiming at refining the clinical management of REPs in accordance with the progress of basic researches and clinical studies, suggesting REPs may become a more consistently evidence-based option in dental treatment.

Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.