Long-term corticosteroid use causes dry mouth by inhibiting calcium movement into salivary gland cells. Corticosteroid use is associated with multiple systemic side effects including salivary inhibition, prompting Yusuke Kondo and a research team from Japan’s Kyushu Dental University to elucidate the reasons why. Submandibular glands taken from mice after six weeks’ treatment with the corticosteroid dexamethasone produced significantly less saliva in ten minutes than a group given just one week’s treatment, or no treatment at all. Further investigation revealed that long-term dexamethasone treatment inhibited the ability of salivary gland cells, known as acinar cells, to transport calcium ions from the exterior to the interior of the cells—an essential mechanism enabling salivation. The study improves our understanding of corticosteroid-induced dry mouth and reveals potential pharmacological targets to enable treatment.

Chronic inflammation damages the collagen disk that cushions the temporomandibular joint (TMJ) of the jaw, contributing to jaw disorders. Although chronic inflammation is known to harm collagen, its effects on TMJ disks were unclear. Xue-Dong Wang and Yan-Heng Zhou and coworkers at the Peking University School and Hospital of Stomatology in Beijing used advanced imaging technologies to investigate how inflammation affects TMJ collagen in rats. In TMJ disks, collagen is composed of long, intertwined threads called fibrils. Inflammation damaged the collagen’s chemical structure, preventing correct winding, and resulting in oversized and unevenly arranged fibrils. The TMJ disks were overly porous, with poor elasticity. The researchers hypothesize that these changes thicken and deform TMJ disks, leading to disk displacement and jaw disorders. Further studies are needed to determine whether anti-inflammatory treatments can protect TMJ collagen.

During embryonic development, the Hedgehog signalling pathway regulates the migration, proliferation and differentiation of cranial neural crest cells in the early frontal bone. The Hedgehog signalling pathway transmits information to embryonic cells for their proper cell differentiation, and increased or reduced function of that signalling results in various craniofacial malformations. A team headed by Weihui Chen at Fujian Medical University in China investigated the patterns of abnormalities caused by inhibition of Hedgehog signalling in pregnant mice at preselected embryonic time points. The team was able to identify the critical period for sensitivity to GDC-0449, a potent Hedgehog signalling inhibitor. The authors believe that their mouse model can be effective in further investigating the mechanisms of craniofacial malformations and will have a profound impact on identifying candidate human disease genes and associated environmental factors.

Using gene-edited cell cultures, Chinese researchers have gathered useful insights into the genetic origins and treatment of benign oral tumours called odontogenic keratocysts (OKCs). A total of 80% of OKCs are associated with mutations in the gene PTCH1, which are thought to activate a signalling pathway that drives OKC tumour growth. However, research is hindered by OKC cell culturing limitations. Tiejun Li, from the Peking University School and Hospital of Stomatology, and colleagues created an OKC cell culture model that uses CRISPR gene editing to introduce a PTCH1 gene mutation into human stem cells before differentiating them into epithelial cells. Using their model, the team confirm that PTCH1 mutation activates tumour-associated signalling, which the basal cell carcinoma drug vismodegib greatly reduces. Vismodegib also reduces the overproliferation of mutant cells and offers a potential treatment option for OKC patients.

In the original version of this Article, Figure 1c was inadvertently assembled with a duplicate of Figure 1b. The correct image for Figure 1c, shown below, has been added in the HTML and PDF versions of the Article. This does not affect the conclusions of the study. We sincerely apologize for any inconvenience this may have caused our readers.

Propolis, also known as ‘honeybee glue,’ may protect teeth and gums against periodontal disease. In periodontal disease, chronic inflammation and oxidative damage harm gum tissue and lead to tooth loss; propolis has been shown to improve periodontal health for patients with diabetes. Bees make propolis by mixing beeswax, honey, plant resins and their own saliva, and use it to patch honeycomb and prevent growth of microbes in the hive. Reinhard Gruber of the Department of Oral Biology at the Medical University of Vienna and of the Department of Periodontology, University of Bern and co-workers investigated the effects of one of propolis’ active ingredients, caffeic acid phenethyl ester (CAPE), on oxidative stress and inflammation. They found that CAPE reduced oxidative damage and dampened inflammation; further investigation revealed the genetic basis of the beneficial effects, paving the way for future clinical studies. These results may help identify alternative treatments for periodontal disease.

Patients with oral cancer have elevated levels of certain protease enzymes in their saliva, a finding that could help with screening and diagnosis. Xuedong Zhou and colleagues from Sichuan University, China, collected saliva samples from patients with different mouth diseases—a type of cancer known as oral squamous cell carcinoma, benign mouth lesions or mild chronic gum disease—as well as healthy controls. They tested the saliva for levels of 35 different proteases, a class of enzymes involved in cleaving proteins, and identified several proteases present only in the saliva of patients with oral cancer, three of which they showed were expressed at high levels in cultured oral tumor cell lines as well. These proteases could thus serve as useful biomarkers in a future spit test for early cancer detection and disease monitoring.

Five pathways for tooth enamel engineering hold great promise for developing new technologies, leading to novel biomaterials and biotechnologies to regenerate enamel tissue. Tooth enamel is a unique tissue-specific biomaterial with exceptional structural and mechanical properties. In recent years, many approaches have been adopted to generate or regenerate this complex tissue; Mirali Pandya and Thomas Diekwisch of Texas A&M College of Dentistry, USA conducted a review of the current state and future directions of enamel tissue engineering. In their review, the authors focused on five pathways for enamel tissue engineering: (1) physical synthesis of enamel; (2) biochemical enamel engineering; (3) in situ enamel engineering; (4) cell-based enamel engineering; and (5) whole tooth regeneration. The authors conclude that those five approaches will help identify the biological mechanisms that lead to the generation of tooth enamel.

Rare diseases are typically genetic, chronic, incurable disorders with a relatively low incidence, and a number of dental and craniofacial manifestations are associated with such diseases. A team headed by En Luo and Hanghang Liu at Sichuan University in China conducted a large-scale review of the manifestations and treatment of rare diseases related to dental and craniofacial disorders. The authors found that in their early stages, several rare diseases exhibit distinctive dental and craniofacial characteristics. Provided they understand the clinical features, dentists and oral surgeons are the individuals best placed to make an early identification of such diseases. The authors believe that their findings will help clinicians fully grasp the related clinical signs and potential treatments of rare diseases, thereby facilitating early diagnosis and patient management as well as improving prognosis.

Swabbing the mouths of germ-free mice with human saliva can provide an effective mouse model for studying the roles of human oral bacteria in mouth and gut diseases. The human oral microbiota-associated (HOMA) mice were developed by Lei Cheng of Sichuan University and colleagues in China and bred alone for 35 days. A significant proportion (85%) of the types of bacteria present in the human donors’ saliva successfully established themselves in the germ-free mice and colonised various parts of their guts. When the HOMA mice were co-bred with other types of mouse models, digestive tract bacteria transferred to them, preventing oral bacteria from significantly colonising the gut. The researchers conclude that a HOMA model was successfully established and could help overcome current limitations in investigations related to human oral bacteria and disease.

Gene therapy targeting a pain receptor in nerve cells carrying signals from the jaw could be an effective treatment for the pain associated with orthodontic treatment. Pain triggered by the movement of teeth is a common reason why patients terminate orthodontic treatment early. Previous studies have suggested that tooth movement is associated with an increase in the expression of transient receptor potential vanilloid 1 (TRPV1), a receptor which is activated by various physical and chemical stimuli, triggering pain. In this study, Wenli Lai at Sichuan University and colleagues confirm that TRPV1 expression increases in response to orthodontic forces which coincide with tooth movement pain in rats. They also show that a lentivirus vector can be used to deliver a small interfering RNA molecule that blocks the expression of TRPV1, alleviating pain.