Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1–34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG’44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.
Aim
To examine the association of life‐style factors, including second‐hand smoke, with dental caries among 3‐year‐old children in Wuxi, China.
Methods
A multi‐stage stratified random cluster sampling method was used, and 283 children were recruited. The prevalence of dental caries was 29.3% (83/283).
Results
Univariate analysis indicated that the possible related factors of dental caries included sleep duration, interest in snacks, candy, exposure to second‐hand smoke and weight of birth (all P < 0.05). Meanwhile, multivariate logistic regression analysis suggested that children who had used fluoride were less susceptible to dental caries than those who had not used fluoride before (P < 0.05). Moreover, the risk of dental caries in children who were very interested in snacks was greater than those with little interest in snacks (P < 0.05).
Conclusions
Life‐style behaviours are crucial factors and should attract enough attention. There might be a potential negative effect of second‐hand smoke on the deciduous caries, but it still requires further studies. A co‐ordinated effort by health‐care providers, policymakers and health institutions has successfully improved children's oral health and the awareness of hygiene knowledge among citizens in Wuxi city.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.