Gab2 plays distinct roles in bone homeostasis at different time points
Gab2 plays distinct roles in bone homeostasis at different time points
复制标题
DOI：
10.1007/s00774-006-0731-y
复制
发表时间：
2007-02
影响因子：
3.3
通讯作者：
S. Itoh;F. Yoshitake;H. Narita;K. Ishihara;S. Ebisu
中科院分区：
文献类型：
--
作者：
S. Itoh;F. Yoshitake;H. Narita;K. Ishihara;S. Ebisu
Grb 2相关结合物2（Gab 2）是一种衔接分子，可被多种生长因子和细胞因子酪氨酸磷酸化。已知Gab 2在调节骨稳态的细胞因子（包括M-CSF、RANKL和IL-6）下游的信号传导途径中起作用。为了阐明Gab 2在骨骼发育不同阶段骨稳态中的作用，我们比较了两个不同年龄的Gab 2 −/−小鼠骨稳态的表型变化。尽管Gab 2 −/−小鼠在两个时间点都表现出骨体积增加，但骨体积增加的原因不同。6周时，骨体积增加是由于骨吸收和骨形成增强，表明Gab 2对破骨细胞生成和成骨细胞分化均起负调节作用。12周时，破骨细胞分化减少导致骨体积增加，表明Gab 2对破骨细胞生成起着积极的调节作用。因此，在骨骼发育和维持阶段，Gab 2在破骨细胞生成中发挥相反的作用。
Grb2-associated binder 2 (Gab2) is an adaptor molecule that can be tyrosine phosphorylated by various growth factors and cytokines. Gab2 is known to play a role in signaling pathways downstream of cytokines that regulate bone homeostasis, including M-CSF, RANKL, and IL-6. To clarify the role of Gab2 in bone homeostasis during distinct phases of skeletal development, we compared phenotypic changes in bone homeostasis inGab2−/−mice at two different ages. AlthoughGab2−/−mice showed increased bone volume at both time points, the reasons underlying the increased bone volume differed. At 6 weeks, the increased bone volume was due to enhanced bone resorption and bone formation, indicating that Gab2 plays a negative regulatory role for both osteoclastogenesis and osteoblast differentiation. At 12 weeks, the increased bone volume resulted from reduced osteoclast differentiation, indicating that Gab2 plays a positive regulatory role for osteoclastogenesis. Thus, Gab2 plays opposite roles in osteoclastogenesis during the phases of skeletal development and maintenance.