Mechanical strain regulates osteoblast proliferation through integrin-mediated ERK activation

• Published in: PloS one Vol. 7; no. 4; p. e35709
• Main Authors: Yan, Yu-xian, Gong, Yuan-wei, Guo, Yong, Lv, Qi, Guo, Chun, Zhuang, Yan, Zhang, Yuan, Li, Ruixin, Zhang, Xi-zheng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.04.2012; Public Library of Science (PLoS)
• Subjects: 3T3 Cells; Activation; Animals; Bending machines; Binding sites; Biocompatibility; Biology; Bone growth; Bone remodeling; Bone remodelling; Bones; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Compression; Deactivation; Enzyme Activation; Experiments; Extracellular matrix; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Gene expression; Gene Expression Profiling; Genes; Growth factors; Homeostasis; Inactivation; Integrin beta Chains - chemistry; Integrin beta Chains - genetics; Integrin beta Chains - metabolism; Integrin beta1 - chemistry; Integrin beta1 - genetics; Integrin beta1 - metabolism; Integrins; Kinases; Load; MAP kinase; Mechanical stimuli; Medical equipment; Mice; Molecular modelling; Osteoblastogenesis; Osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; Periodic variations; Periodicity; Phosphorylation; Physiology; Protein kinase; Protein kinases; Proteins; Quality control; Receptors; RNA Interference; RNA, Small Interfering - metabolism; Science; Shear stress; Signal transduction; Signal Transduction - drug effects; Signaling; Stem cells; Strain; Stress, Mechanical; Studies; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035709

Mechanical strain plays a critical role in the proliferation, differentiation and maturation of bone cells. As mechanical receptor cells, osteoblasts perceive and respond to stress force, such as those associated with compression, strain and shear stress. However, the underlying molecular mechanisms of this process remain unclear. Using a four-point bending device, mouse MC3T3-E1 cells was exposed to mechanical tensile strain. Cell proliferation was determined to be most efficient when stimulated once a day by mechanical strain at a frequency of 0.5 Hz and intensities of 2500 µε with once a day, and a periodicity of 1 h/day for 3 days. The applied mechanical strain resulted in the altered expression of 1992 genes, 41 of which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of ERK by mechanical strain promoted cell proliferation and inactivation of ERK by PD98059 suppressed proliferation, confirming that ERK plays an important role in the response to mechanical strain. Furthermore, the membrane-associated receptors integrin β1 and integrin β5 were determined to regulate ERK activity and the proliferation of mechanical strain-treated MC3T3-E1 cells in opposite ways. The knockdown of integrin β1 led to the inhibition of ERK activity and cell proliferation, whereas the knockdown of integrin β5 led to the enhancement of both processes. This study proposes a novel mechanism by which mechanical strain regulates bone growth and remodeling.