Identifying the nerve pathways involved in tooth movement could lead to better targets for pain relief. Non-steroidal anti-inflammatory drugs cannot be used to relieve orthodontic pain because they impair the processes involved in tooth movement. Yoshiko Ariji of Japan’s Aichi-Gakuin University School of Dentistry, Nagoya, and colleagues used functional MRI scans of ten healthy adult volunteers to identify the parts of the brain that become active when separators are briefly inserted between pre-molar teeth. They found separator insertion led to a significant rise in the activity of the hypothalamus and the part of the brain’s cerebral cortex associated with touch and proprioception. Together with the results of previous studies in mice, the results suggest a nerve pathway that could be targeted to alleviate pain from orthodontic procedures without negatively impacting tooth movement.
The damage from oral infection with the fungus Candida albicans can be contained by targeting two cell membrane-building genes. C. albicans cells transition from a rounded shape into long filamentous structures called hyphae prior to invading and damaging host epithelial cells. Researchers led by Lei Cheng at Sichuan University have now identified a key intermediate step between hyphae formation and virulence. They determined that fungal cells lacking either of two genes that manufacture ergosterol, a component of the C. albicans membrane, still form hyphae and attach to epithelial cells. However, these mutant fungi inflict no cellular damage, and did not cause disease in mice. Furthermore, treatment with low-dose fluconazole, a drug that inhibits ergosterol synthesis, rendered the fungus non-virulent without killing it, indicating that this pathway represents an important ‘missing link’ for fungal pathogenesis.
New imaging technologies hold promise for early detection and improved treatment of head and neck cancers, the sixth most common type of cancer worldwide. The first line of treatment is surgery, but complete tumor removal can be difficult when operating on this sensitive region. Improving methods for early detection and clear visualization of tumor edges could help minimize loss of healthy tissue. Eben Rosenthal at Stanford University in California and Yi Li at the West China School of Stomatology in Chengdu City reviewed new technologies, many of which use fluorescence to identify tumor tissue. Some techniques even allow real-time visualization of tumor edges in the operating theatre. The researchers discuss the applications and limitations of these new technologies and highlight promising future directions, including increasing the commercial availability and decreasing the size of the instruments.
A pretreatment procedure that creates a porous, mineral-coated surface on dental implants leads to superior integration into bone. Micro-arc oxidation (MAO) can be used to apply thick coatings enriched in phosphorus and calcium onto titanium implants. Researchers led by Baodong Zhao of The Affiliated Hospital of Qingdao University in China have demonstrated that this complex three-dimensional surface offers a supportive environment for bone growth. Zhao and colleagues examined the integration of MAO-treated titanium implants into the femurs of live rabbits relative to implants with smooth surfaces. After 12 weeks, MAO promoted more active bone formation and mineral deposition, and the researchers observed that bone cells readily penetrated the porous surface of these implants to enable extensive skeletal integration. These results suggest that this procedure might meaningfully improve the outcome of dental procedures in the clinic.
Targeting a protein complex involved in the body’s response to low internal oxygen concentrations could help treat destructive tooth root inflammations. Hajime Sasaki from the University of Michigan and colleagues in the U.S. and Japan investigated the role of the protein complex HIF-1 in oral inflammation. They induced lesions in the root area of molar teeth in mice, exposing them to oral bacteria, which led to inflammation. They injected the mice with one of two agents that activate the HIF-1 pathway. Inflammation and bone destruction in the lesions were both reduced. Activation of the HIF-1 pathway turned off another pathway, called NF-κB, involved in the immune response to infection. It also turned off genes involved in bone destruction. The results indicate that HIF-1 has a protective effect on tooth root lesions and could play a role in their treatment pending further investigations.
Therapies targeting a cartilage-regulating signaling protein could mitigate painful damage inflicted on the jaw by age-related osteoarthritis. Many older individuals experience degeneration of the temporomandibular joint (TMJ), where the upper and lower jaw connect. Researchers led by Di Chen of Rush University Medical School in Chicago, USA, have developed a genetically-modified mouse model that reveals a likely molecular driver for TMJ osteoarthritis. Previous studies have implicated a protein called β-catenin in this process, and Chen’s team generated mice in which β-catenin levels can be selectively boosted in cartilage-forming cells at skeletal joints. This increased β-catenin markedly altered the organization of TMJ cartilage, with decreased cell proliferation and increased cell death. The effects were strikingly similar to human osteoarthritis, and the researchers hypothesize that compounds that counter β-catenin could offer useful treatments for this condition.
Regenerated nerves play a role in restoring the function of transplanted submandibular glands (SMGs) in treating dry eye syndrome. Dry eye syndrome, or keratoconjunctivitis sicca (KCS), is a leading cause of patients visiting ophthalmologists, and one effective treatment in severe cases is transplanting SMGs (to the temporal area). Autonomic nerves have an important function in maintaining the secretory function of salivary glands, and a team headed by Yan Zhang and Guang-Yan Yu at Peking University, China investigated whether those nerves underwent reinnervation (restoration of nerve control) with transplanted SMGs in KCS patients and in a rabbit model. The authors found that in both the patients and rabbit model, the transplanted SMGs were reinnervated and the regenerated nerves played a role in restoring the glands’ function. The findings offer new insights into managing SMG transplantation.
A protein with its roots in dental development stimulates the proliferation and gene expression of cells linked to regeneration. Amelogenin is a mediator of enamel and tooth root formation, and the main component of a recently-developed medicine for periodontal regeneration. An international research group led by Sema Hakki, of Selcuk University, Turkey, has now elucidated the effects of amelogenin on cementoblasts, a type of cell responsible for producing the vital, mineralized layer on surface of the tooth root. Hakki’s team found that the bacteria-derived amelogenin increased the rate of mouse cementoblast proliferation and mineralization in vitro, and increased the expression of genes related to bone and tissue generation. The team also demonstrated the presence of a likely amelogenin receptor on the cells used in their study. These findings support further investigation into amelogenin’s therapeutic potential.
A new resource for consolidating oral microbiome data will help researchers explore the relationship between these commensal communities and the health of their hosts. Numerous studies have highlighted apparent connections between alterations in the microbial communities within the human mouth and medical conditions including diabetes and cancer. A recent article from researchers led by Liao Ga at Sichuan University describes the launch of the Oral Microbiome Bank of China, an effort to study such connections by profiling specimens from individuals from across the country. The database currently houses detailed information on 289 bacterial strains and the samples from which they were obtained. The authors are now looking to analyze these data to gain insights into the structure and function of oral ecosystems, and to further expand this database as a resource for Chinese microbiome research.
Magnetic resonance imaging (MRI) can differentiate between periapical (apex of a tooth root) cysts and granulomas (inflammations usually caused by infections). MRI is a radiation-free, non-invasive imaging technique, and a team headed by Tim Hilgenfeld at Heidelberg University Hospital in Germany conducted a pilot study to determine whether dental MRI could be used to distinguish periapical cysts from granulomas in 11 patients with confirmed periapical lesions. The authors found that dental MRI allowed for the identification of six characteristics, each of which had the capacity to clearly differentiate between periapical cysts and granulomas. The team’s findings need to be confirmed in future studies with larger numbers of patients. But the results could have a substantial clinical impact in improving diagnoses and avoiding unnecessary surgery in patients with periapical lesions.
A strong, long-lasting bonding agent developed by researchers in the US and China can protect tooth restorations from bacteria and proteins. Tooth restorations often fail due to recurrent decay which starts when bacteria invade the interface between the tooth and the restoration material, producing acids. To combat this problem, Ning Zhang at the University of Maryland, Baltimore, and Capital Medical University, Beijing, and co-workers infused the commercial Scotchbond Multi-Purpose primer and adhesive with two chemicals known to inhibit the formation of bacterial biofilms. The team stored bonded teeth in warm water for six months, after which they found no decline in the bond strength, or its resistance to oral proteins and bacteria. They hope that by incorporating the same protective chemicals into cements, composites and sealants, failure rates in tooth restorations could be reduced.
A Chinese herbal supplement could treat an inflammatory autoimmune disease of the tissues surrounding the teeth. Zhipeng Fan and colleagues at Capital Medical University in Beijing, China found reduced inflammation and improved tissue regeneration in induced periodontitis in miniature pigs, three months following local injections with the Chinese herbal extract icariin. Periodontitis is an overactive immune response to bacterial invasion in the gums, leading to the breakdown of supportive tissue and bone, and potential tooth loss. Clinical assessment, CT scans and microscopic examination showed icariin injections promoted gum and bone regeneration, possibly by stimulating local stem cells. It also reduced signs of inflammation, including significantly decreasing the expression of IL-1β, an immune response mediator. Further studies are needed to confirm icariin’s mode of action and optimal dosage for potential clinical use.
‘Bone-conditioned medium’ could improve oral bone regeneration therapy by promoting the proliferation and maturation of bone-forming cells. Building on recent research demonstrating the benefits of using cell culture medium prepared with bone chips (BCM) in such treatments, researchers led by Maria Asparuhova of the University of Bern, Switzerland, set out to elucidate the medium’s mechanisms. The team found that BCM incubated with bone chips for short periods—as little as ten minutes—contained heightened levels of signaling protein TGF-β1, which enhanced mouse bone marrow cell proliferation while downregulating maturation. BCM incubated for longer periods also generated increased levels of another protein, BMP-2, which boosted the maturation of bone-forming cells. This study reveals a sequential role of these two factors in oral bone development, and the potential physiological actions of BCM when used in regenerative therapies.