State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Cell Physiol. 2019 Jul;234(7):11900-11911. doi: 10.1002/jcp.27857. Epub 2018 Dec 24.
Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/β-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/β-catenin pathway.
牙滤泡细胞 (DFC) 在牙齿发育和出牙过程中激活并招募破骨细胞,而 DFC 本身通过与 Hertwig 上皮根鞘 (HERS) 的相互作用分化为成骨细胞,形成围绕牙根的牙槽骨。在牙齿发育过程中,甲状旁腺激素相关肽 (PTHrP) 在牙胚周围表达。因此,我们旨在研究 PTHrP (1-34) 对体外和体内 DFC 骨吸收和骨生成的影响。体外研究表明,与 HERS 细胞共培养的 DFC 表达的 BSP 和 OPN 水平高于 DFC 对照组,而用 PTHrP (1-34) 处理的共培养 DFC 的 ALP、RUNX2、BSP 和 OPN 表达低于共培养 DFC 对照组。此外,我们发现 PTHrP (1-34) 通过抑制 Wnt/β-catenin 通路抑制共培养 DFC 的成骨作用。PTHrP (1-34) 还增加了 DFC 中 RANKL/OPG 比值的表达。同样,体内研究发现 PTHrP (1-34) 加速了牙齿的萌出并抑制了牙槽骨的形成。因此,这些结果表明 PTHrP (1-34) 通过抑制 Wnt/β-catenin 通路加速牙齿萌出并抑制 DFC 的成骨作用。
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