Gestational diabetes mellitus affects odontoblastic differentiation of dental papilla cells via Toll‐like receptor 4 signaling in offspring

• Published in: Journal of cellular physiology 2020-04, Vol.235 (4), p.3519-3528
• Main Authors: Lyu, Yun, Jia, Sixun, Wang, Shikang, Wang, Tao, Tian, Weidong, Chen, Guoqing
• Format: Article
• Language: English
• Subjects: Animals; Calcification, Physiologic - genetics; Cell differentiation; Cell Differentiation - genetics; Cell Proliferation - drug effects; Dental Papilla - growth & development; Dental Papilla - metabolism; dental papilla cells; Dental Pulp - growth & development; Dental Pulp - pathology; Dentin; Diabetes; Diabetes mellitus; Diabetes, Gestational - genetics; Diabetes, Gestational - pathology; Differentiation; Female; gestational diabetes mellitus; Humans; NF-kappa B - genetics; odontoblast; Odontoblasts; Odontoblasts - metabolism; Offspring; Pathogenesis; Phosphorylation; Phosphorylation - genetics; Pregnancy; Rats; Signal transduction; Signal Transduction - genetics; Signaling; Smad1 Protein; Streptozocin; Sulfonamides - pharmacology; Teeth; TLR4 protein; TLR4/NF‐ĸB signaling; Toll-Like Receptor 4 - genetics; Toll-like receptors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29240

Gestational diabetes mellitus (GDM) is an important factor involved in the pathogenesis of organ development in the offspring. Here, we analyzed the effects of GDM on odontoblastic differentiation of dental papilla cells (DPCs) and dentin formation in offspring and investigated their underlying mechanisms. A GDM rat model was induced by intraperitoneal injection of streptozotocin and offspring were collected. The results showed that GDM significantly affected odontoblast differentiation and dentin formation in offspring tooth. GDM activated the toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐ĸB) signaling pathway and inhibited SMAD1/5/9 signaling to modulate the odontoblastic differentiation of DPCs in offspring. Inhibition of TLR4 signaling by treated with TAK‐242 significantly reverses the suppression of odonto‐differentiation of DPCs in diabetic offspring. Taken together, these data indicate GDM activated the offspring DPCs TLR4/NF‐ĸB signaling, which suppressed the SMAD1/5/9 phosphorylation and then inhibited odontoblasts differentiation and dentin formation. Maternal gestational diabetes activated the offspring dental papilla cells TLR4/nuclear factor‐kappa B signaling, which suppressed the SMAD1/5/9 phosphorylation and then inhibited odontoblasts differentiation and dentin formation of offspring.