PIEZO1 Promotes Odontoblast-Mediated Reactionary Dentinogenesis via SEMA3A.

Located at the interface of the dentin-pulp complex, the odontoblasts are specialized cells responsible for dentin synthesis and nociceptive signal detection in response to external stimuli. Recent studies have shown that the mechanosensitive ion channel PIEZO1 is involved in bone formation and remodeling through the influx of calcium ions, and it is abundantly expressed in odontoblasts. However, the specific role of PIEZO1 in reactionary dentinogenesis and the underlying mechanisms remain elusive. In this study, we found intense PIEZO1 expression in the plasma membrane and cytoplasm of odontoblasts in healthy human third molars, mouse mandibular molars, and human odontoblast-like cells (hOBLCs). In hOBLCs, PIEZO1 positively regulated DSPP, DMP1, and COL1A1 expression through the Ca2+/PI3K-Akt/SEMA3A signaling pathway. In addition, exogenous SEMA3A supplementation effectively reversed reduced mineralization capacity in PIEZO1-knockdown hOBLCs. In vivo, Piezo1 expression peaked at day 7 and returned to baseline at day 21 in a wild-type mice dentin injury model, with Sema3a presenting a similar expression pattern. To investigate the specific role of PIEZO1 in odontoblast-mediated reactionary dentinogenesis, mice with a conditional knockout of Piezo1 in odontoblasts were generated, and no significant differences in teeth phenotypes were observed between the control and conditional knockout (cKO) mice. Nevertheless, cKO mice exhibited reduced reactionary dentin formation and decreased Sema3a and Dsp positive staining after dentin injury, indicating impaired dental pulp repair by odontoblasts. In summary, these findings suggest that PIEZO1 enhances the mineralization capacity of hOBLCs in vitro via the Ca2+/PI3K-Akt/SEMA3A signaling pathway and contributes to reactionary dentinogenesis in vivo.

[Influence of vascular risk factors on seasonality of benign paroxysmal positional vertigo].

Objective: To investigate the seasonal changes of benign paroxysmal positional vertigo (BPPV) onset, and explore the relationship between vascular risk factors and the seasonal patterns of BPPV. Methods: Data of 3 886 patients subjected to vestibular function examination and diagnosed with BPPV who underwent manipulation or instrumental repositioning from January 1, 2016 to December 31, 2019 in the Department of Neurology, Beijing Tiantan Hospital were retrospectively analyzed. Demographic information and medical history of the patients were recorded. Weather temperature data of Beijing were obtained and monthly averages were calculated. The relationship between the BPPV onset and temperature and seasonality was investigated. Meanwhile, the influence of vascular risk factors on the seasonal patterns of BPPV was determined. Results: BPPV is more common in women (n=2 667). The male to female ratio of patients was approximately 1∶2, with a mean age of (55±13) years. The cases of BPPV in spring (March-May), summer (June-August), autumn (September-November) and winter (December-February) were 1 000 (25.7%), 911 (23.4%), 808 (20.8%) and 1 167 (30.0%), respectively. The peak incidence of BPPV occurred in December (n=491) and the lowest occurred in September (n=251). The number of BPPV cases diagnosed monthly was inversely correlated with mean temperature (R2=0.317; P<0.001). Patients with ≥2 vascular risk factors were at higher risk of developing BPPV in spring or winter than those without risk factors (OR=1.32, 95%CI: 1.13-1.53,P<0.001). Proportion of onset in spring or winter increased with each additional risk factor (P trend<0.001). Conclusions: BPPV often occurs in the months with low temperature (spring and winter) and the number of cases is inversely correlated with temperature. Compared with those with no vascular risk factors, patients with more vascular risk factors are more likely to develop BPPV in spring and winter.