Sclerotic dentin is a natural self-protective barrier beneath non-carious cervical lesions (NCCLs), which are mainly induced by mechanical stress. Sclerostin is a mechanosensory protein and serves as an inhibitor of dentinogenesis. However, its function on mechanotransduction in dentine-pulp complex has not been elucidated yet. In this study, decreased sclerostin expression was detected in odontoblasts beneath NCCL-affected sclerotic dentin. Then human pulp-derived odontoblast-like cells (hOBs) were subjected to mechanical strain (MS) in vitro: the results showed that MS-induced upregulation of odontogenic differentiation markers (dentin sialophosphoprotein, osteopontin, osteocalcin, and runt-related transcription factor 2) in hOBs with downregulated sclerostin expression, and this inductive differentiation was attenuated when sclerostin was overexpressed. Additionally, MS activated ERK1/2 pathway and ERK1/2 inhibition restored MS-induced downregulation of sclerostin. Proteasome inhibitor MG132 could also rescue MS-induced decrease of sclerostin. Furthermore, MS suppressed STAT3 pathway, which could be reversed by sclerostin overexpression. STAT3 inhibition was shown to ameliorate the reduction of odontogenic markers induced by sclerostin overexpression. Taken together, we conclude that MS downregulates sclerostin expression via the ERK1/2 and proteasome signaling pathways to promote odontogenic differentiation of hOBs through the STAT3 signaling pathway. It can therefore be inferred that under mechanical stress, sclerostin inhibition promotes reactive dentin formation by enhancing odontogenic differentiation of odontoblasts, which might be one of potential forming mechanisms of sclerotic dentin beneath NCCLs. K E Y W O R D SERK1/2, mechanotransduction, proteasome pathway, sclerostin, sclerotic dentin, SOST, STAT3

Sclerostin is the protein product of the SOST gene and is known for its inhibitory effects on bone formation. The monoclonal antibody against sclerostin has been approved as a novel treatment method for osteoporosis. Oral health is one of the essential aspects of general human health. Hereditary bone dysplasia syndrome caused by sclerostin deficiency is often accompanied by some dental malformations, inspiring the therapeutic exploration of sclerostin in the oral and dental fields. Recent studies have found that sclerostin is expressed in several functional cell types in oral tissues, and the expression level of sclerostin is altered in pathological conditions. Sclerostin not only exerts similar negative outcomes on the formation of alveolar bone and bone-like tissues, including dentin and cementum, but also participates in the development of oral inflammatory diseases such as periodontitis, pulpitis, and peri-implantitis. This review aims to highlight related research progress of sclerostin in oral cavity, propose necessary further research in this field, and discuss its potential as a therapeutic target for dental indications and regenerative dentistry.

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Background The COVID-19 pandemic has changed the learning style and campus life of dental students. This study aimed to evaluate the learning attitudes and outcomes of endodontics among mainland Chinese students and non-mainland Chinese students (students from Hong Kong, Macao, and Taiwan) during the pandemic. Methods A cross-sectional survey was conducted in November 2022 at the School of Stomatology, Jinan University, utilizing a self-report online questionnaire, including demographic characteristics and attitudes toward the endodontic course and the COVID-19 pandemic. The endodontics scores were collected from recruited students for further analysis. The collected data were analyzed using SPSS 22.0 software, with independent two-sample t-tests to compare continuous variables and chi-square tests for categorical variables. Results A total of 215 dental students completed the survey, with 126 (58.6%) of them being non-mainland Chinese students. Compared to mainland Chinese students, non-mainland Chinese students had lower scores in both theoretical (63.6 ± 13.5 vs. 83.2 ± 8.00) and skill (88.4 ± 5.38 vs. 90.0 ± 4.91) endodontic assessments. Non-mainland Chinese students reported significantly greater impacts of the COVID-19 pandemic on their learning emotions, personal hygiene, and future career choices compared to mainland Chinese students. Conclusions Non-mainland Chinese students had poorer academic performance in endodontics and experienced a greater impact from the COVID-19 pandemic in terms of their studies and lives. Dental educators should consider the diversity of students and take necessary measures to support their mental health and enhance learning outcomes in the post-COVID-19 era.