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

Spry2显性阴性突变体（Y55A-Spry2）的转导增强了MC3T3-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GE1细胞中的激活。与这些观察结果一致，Y55A-Spry2在bFGF和EGF刺激下增加了成骨细胞的增殖，而Y55A-Spry2引入的GE1细胞的增殖通过EGF受体（egfr）的泛素化和降解而降低。此外，Y55A-Spry2在bFGF和EGF的作用下，导致Runx2负调控因子Twist表达上调，Runx2负调控因子Twist表达下调，导致MC3T3-E1细胞成骨增强，碱性磷酸酶激活，骨钙素表达增强。

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.