Calcium regulates the PI3K‐Akt pathway in stretched osteoblasts

FEBS Letters

Hauschka, Peter V²  Freeman, Michael R¹  Naruse, Keiji³  Adam, Rosalyn M¹  Danciu, Theodora E² 

[1] The Urologic Laboratory, Department of Urology, Children's Hospital Boston, and the Department of Surgery, Harvard Medical School, Boston, MA 02115, USA;Department of Orthopaedic Surgery, John F. Enders Research Laboratories, Room 1230, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA;Department of Physiology, Nagoya University School of Medicine, and Cell Mechanosensing Project, ICORP, JST, Nagoya, Japan

关键词: Osteoblast;    Stretch;    Calcium;    Akt;    Stress-activated protein kinase/c-Jun N-terminal kinase;   

DOI  :  10.1016/S0014-5793(03)00055-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mechanical loading plays a vital role in maintaining bone architecture. The process by which osteoblasts convert mechanical signals into biochemical responses leading to bone remodeling is not fully understood. The earliest cellular response detected in mechanically stimulated osteoblasts is an increase in intracellular calcium concentration ([Ca²⁺]_i). In this study, we used the clonal mouse osteoblast cell line MC3T3-E1 to show that uniaxial cyclic stretch induces: (1) an immediate increase in [Ca²⁺]_i, and (2) the phosphorylation of critical osteoblast proteins that are implicated in cell proliferation, gene regulation, and cell survival. Our data suggest that cyclic stretch activates the phosphoinositide 3-kinase (PI3K) pathway including: PI3K, Akt, FKHR, and AFX. Moreover, cyclic stretch also causes the phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase. Attenuation in the level of phosphorylation of these proteins was observed by stretching cells in Ca²⁺-free medium, using intra- (BAPTA-AM) and extracellular (BAPTA) calcium chelators, or gadolinium, suggesting that influx of extracellular calcium plays a significant role in the early response of osteoblasts to mechanical stimuli.

【 授权许可】

Unknown