Mechanisms of Fgf18 Signaling in the Tooth Pulp

成纤维细胞生长因子（Fibroblastgrowthfactor，Fgf）18是Fgf 8家族的成员，与骨和软骨的形成有关。结果表明，Fgf18在大鼠牙髓组织中有高表达。本研究假设Fgf 18在牙髓分化和功能中起重要作用，首先检测了Fgf 18在牙髓和牙齿发育过程中的表达。用Fgf18的特异性探针进行原位杂交，发现Fgf18的表达首先见于帽状期和钟状期的牙乳头。Fgf18在芽期不表达。在帽状期和钟状期的牙乳头中也检测到Fgf受体2c和3c，提示Fgf 18诱导的Fgf信号通路在帽状期和钟状期的牙乳头中起着积极的作用。应用FGF 18促进牙髓细胞在体外的细胞生长。FGF18诱导的细胞生长与FGF2诱导的细胞生长相似。矿化标记物如碱性磷酸酶的表达被FGF18下调。提示Fgf 18的主要功能是促进牙髓细胞生长，可能是维持牙髓内环境稳定的重要因素之一。

Fibroblast growth factor (Fgf) 18 is a member of Fgf8 family, and it is relating to thebone and cartilage formation. I revealed that Fgf18 was highly expressed in rat dentalpulp tissues using cDNA macro-array. I hypothesized that Fgf18 had important roles inpulpal differentiation and function.Expression of Fgf18 in the pulpal and tooth development was evaluated at first. Insitu hybridization using a specific probe of Fgf18 revealed that Fgf18 expression was first observed in the dental papillae of cap and bell stages. No expression of Fgf18 was detected in the bud stage. Fgf receptor 2c and 3c, which are receptors against Fgf18, was also detected in the dental papillae of cap and bell stages, which suggested thatthe Fgf signaling induced by Fgf18 was actively working in the dental papillae of these stages. Application of FGF18 to the pulpal cells promoted cell growth in vitro. The cell growth induced by FGF18 was similar to that induced by FGF2. Expression of mineralizing markers, such as alkaline phosphatase, was down-regulated by FGF18. These data indicated that major function of Fgf18 should be pulpal ell growth, and it may be one of important factors to maintain the pulpal homeostasis.