Inhibition of Spry2 Induces Proliferation and Differentiation of Osteoblasts through bFGF and EGF Stimulation but Inhibits Proliferation of Gingival Epithelial Cells.

Spry 2的显性负突变体（Y55 A-Spry 2）的转导增强了MC 3 T3-E1成骨细胞中碱性成纤维细胞生长因子（bFGF）和表皮生长因子（EGF）诱导的ERK活化。相反，它降低了它们在GE 1细胞中的活化。与这些观察结果一致，Y55 A-Spry 2增加成骨细胞增殖与bFGF和EGF刺激，而增殖的Y55 A-Spry 2引入GE 1细胞通过泛素化和降解的EGF受体（EGFR）减少。此外，Y55 A-Spry 2引起Runx 2表达的上调和Twist（Runx 2的负调节物）的下调，用bFGF和EGF处理，导致MC 3 T3-E1细胞中成骨细胞生成增强，伴随碱性磷酸酶活化和骨钙素表达。

Transduction of a dominant-negative mutant of Spry2 (Y55A-Spry2) enhanced basic fibroblast growth factor (bFGF)- and epidermal growth factor (EGF)-induced ERK activation in MC3T3-E1 osteoblastic cells. In contrast, it decreased their activation in GE1 cells. Consistent with these observations, Y55A-Spry2 increased osteoblast proliferation with bFGF and EGF stimulation, whereas the proliferation of Y55A-Spry2-introduced GE1 cells was decreased via the ubiquitination and degradation of EGF receptors (EGFRs). In addition, Y55A-Spry2 caused upregulation of Runx2 expression and downregulation of Twist, a negative regulator of Runx2, with treatment of bFGF and EGF, resulting in enhanced osteoblastogenesis accompanied by alkaline phosphatase activation and osteocalcin expression in MC3T3-E1 cells.