Title | Osteoblastic molecular scaffold Gab1 is required for maintaining bone homeostasis |
Authors | Weng, Tujun Mao, Fengfeng Wang, Youliang Sun, Qiang Li, Ruixin Yang, Guan Zhang, Xizheng Luo, Jincai Feng, Gen-Sheng Yang, Xiao |
Affiliation | Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing 100071, Peoples R China. Acad Tianjin Med Sci, Inst Med Equipment, Tianjin 300161, Peoples R China. Peking Univ, Lab Vasc Biol, Inst Mol Med, Beijing 100871, Peoples R China. Univ Calif San Diego, Dept Pathol, Sch Med, La Jolla, CA 92037 USA. Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92037 USA. Shanghai Jiao Tong Univ, E Inst Shanghai Univ, Model Organism Div, Shanghai, Peoples R China. |
Keywords | Gab1 Osteoblast Bone mass AKT ERK Apoptosis ACTIVATED PROTEIN-KINASE GROWTH-FACTOR COLLAGEN-SYNTHESIS SIGNALING PATHWAY GRB2-ASSOCIATED BINDER-1 TYROSINE PHOSPHATASE SKELETAL DEVELOPMENT EPIDERMAL-GROWTH DOCKING PROTEIN CELL-SURVIVAL |
Issue Date | 2010 |
Publisher | journal of cell science |
Citation | JOURNAL OF CELL SCIENCE.2010,123,(5),682-689. |
Abstract | The Grb2-associated binder 1 (Gab1), which serves as a scaffolding adaptor protein, plays a crucial role in transmitting key signals that control cell growth, differentiation and function from multiple receptors. However, its biological role in osteoblast activity and postnatal bone metabolism remains unclear. To elucidate the in vivo function of Gab1 in postnatal bone remodeling, we generated osteoblast-specific Gab1 knockout mice. Disruption of Gab1 expression in osteoblasts led to decreased trabecular bone mass with a reduced bone formation rate and a decreased bone resorption. Bones from Gab1 mutants also exhibited inferior mechanical properties. Moreover, primary osteoblasts from Gab1 mutant mice demonstrated markedly suppressed osteoblast mineralization, increased susceptibility to apoptosis and decreased expression of receptor activator of NF-kappa B ligand (RANKL). Activation of serine-threonine Akt kinase and extracellular signal-regulated kinase in response to insulin and insulin-like growth factor 1 was attenuated in Gab1 mutant osteoblasts. Our results show that Gab1-mediated signals in osteoblasts are crucial for normal postnatal bone homeostasis. |
URI | http://hdl.handle.net/20.500.11897/395919 |
ISSN | 0021-9533 |
DOI | 10.1242/jcs.058396 |
Indexed | SCI(E) |
Appears in Collections: | 分子医学研究所 |