The hormone helps in the regeneration of bone tissue that supports teeth.

Discovery was made from RNA sequencing of stem cells in the oral region

A report by the United Nations (UN) reveals that almost half of the world's population, around 45%, is affected by oral diseases. Among these conditions, periodontal diseases are particularly serious, and can lead to inflammation of the gums and, in advanced cases, periodontitis. This infection can destroy the alveolar bone, causing serious problems, such as tooth loss.

Although there are regenerative techniques to try to stop and reverse this damage, they often have a limited effect and are not always effective in periodontal clinics. This is due, in part, to the lack of knowledge about the cellular processes that can contribute to the regeneration of the bone tissues responsible for supporting the teeth.

Aware of the need for more research in this area, Catharina Marques Sacramento decided to investigate the RNA sequencing of stem cells in dental tissue during her doctorate, carried out at the Piracicaba School of Dentistry (FOP) at Unicamp. Sacramento discovered that the hormone cholecystokinin (CCK) plays a crucial role in tissue mineralization, a process essential for the formation of bone that supports teeth.

Her study was recognized with the Hatton Prize in the Research Innovation category during the 2023 congress of the International Association for Dental Research (IADR). The award highlighted the importance of the discoveries made during her doctorate, carried out under the supervision of Professor Karina Gonzales Silvério Ruiz, from the Department of Prosthetics and Periodontics at FOP.

The Sacramento research followed on from previous research conducted by Ruiz with the aim of understanding what gave a stem cell the potential to form mineralized tissue. The professor, together with another former advisor, had already performed RNA sequencing in previous research, but only part of that data had been explored.

“The previous research generated a large volume of data, and it was from this data that Catharina began to work, offering a new perspective,” explains Ruiz. During her analysis of the genetic sequencing, Sacramento identified an unusual cell signaling pathway in the oral region, which had never been associated with the formation of tissue in the oral cavity. Until then, this pathway had been linked to gastrointestinal problems, according to published studies.

Cell signaling pathways form “communication routes” within cells, allowing us to indicate which hormones or other substances are needed in response to stimuli. “Normally, when analyzing bone cells, we consider the classic cell signaling pathways, which have already been widely studied. I decided to investigate something new: the cholecystokinin hormone pathway, which the sequencing results showed to be present in bone cells of the periodontal ligament, despite the literature associating it mainly with the gastrointestinal system. This aroused my curiosity. I wondered what it was doing there,” explains Sacramento.

In addition to this point, the student says, the characteristics of the CCK pathway were similar to another pathway known for its relationship with bone production. “Since the CCK pathway was similar to the calcium pathway, I reviewed the literature and raised the hypothesis that CCK is important for bone formation,” she adds.

Based on this hypothesis, Sacramento conducted pilot experiments and demonstrated that the hormone CCK is important for the production of bone tissue in the oral region. However, in order to validate the discovery, additional studies were necessary.

The researcher then tested, through in vitro experiments , drugs intended for the gastrointestinal system that stimulate or block the production of CCK in cells of the oral cavity and found that the hormone was directly related to the formation of bone tissue.

“This was a very interesting finding, as no one had observed this before. Professor Karina and I value innovation and the possibility of discovering something that could have a significant impact. The idea that something related to the gut could be applicable in the mouth was phenomenal. When we started seeing the results, we realized the great potential for clinical applications,” says Sacramento.

Although there is still a long way to go, both the student and her supervisor believe in the potential for clinical application, not only in dentistry, but also in medicine in general. “We are confirming our results in several ways, not only in periodontal ligament cells. We have also observed that CCK may be important in bone mineralization in other parts of the body,” she explains. Neither of them rule out the possibility that the results found may encourage doctors to turn their attention to this hormone.

Currently, Sacramento is in the Postdoctoral Researcher Program at FOP, where he teaches undergraduate and graduate courses. He is preparing to continue his postdoctoral research, which will focus on developing a biomaterial capable of stimulating hormone production in the oral region, first with in vitro tests , then in animals and, depending on the results, in humans.

The work has already generated new research avenues for Ruiz's students, from undergraduate research to doctoral studies, and continues to be a source of encouragement and inspiration for other students. One of the planned collaborations involves a partnership with a biomaterials development laboratory at the University of Oregon (United States), which is submitting a project to the São Paulo Research Foundation (FAPESP).