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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chida, Toko Sasaki, Keiichi Takeda, Kohsuke Fukuno, Naoto Nagaura, Yuko Kanda, Yoshiaki Nishitoh, Hideki Tamura, Shinri Ichijo, Hidenori Kobayashi, Takayasu Matsui, Hiroyuki Kantoh, Yusuke Sawada, Yasuhiro Suzuki, Osamu |
| Description | Author Affiliation: Matsui H ( From the Department of Biochemistry, Institute of Development, Aging and Cancer.) |
| Abstract | Bone mass is maintained by the balance between the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. It is well known that adequate mechanical stress is essential for the maintenance of bone mass, whereas excess mechanical stress induces bone resorption. However, it has not been clarified how osteoblasts respond to different magnitudes of mechanical stress. Here we report that large-magnitude (12%) cyclic stretch induced Ca(2+) influx, which activated reactive oxygen species generation in MC3T3-E1 osteoblasts. Reactive oxygen species then activated the ASK1-JNK/p38 pathways. The activated JNK led to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, the ASK1-p38 pathway induced expression of the monocyte chemoattractant protein 3 (MCP-3) gene, which promoted chemotaxis of preosteoclasts. In contrast, the ERK pathway was activated by small-magnitude stretching (1%) and induced expression of two osteogenic genes, collagen Ia (Col1a) and osteopontin (OPN). Moreover, activated JNK suppressed Col1a and OPN induction in large-magnitude mechanical stretch-loaded cells. The enhanced expression of Fn14 and MCP-3 by 12% stretch and the enhanced expression of Col1a and OPN by 1% stretch were also observed in mouse primary osteoblasts. These results suggest that differences in the response of osteoblasts to varying magnitudes of mechanical stress play a key role in switching the mode of bone metabolism between formation and resorption. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 10 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-03-07 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Gene Expression Regulation MAP Kinase Kinase Kinase 5 Metabolism Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinase 9 Osteoblasts Physiology Receptors, Tumor Necrosis Factor Genetics Stress, Mechanical 3T3 Cells Animals MAP Kinase Signaling System Mice Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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