title: Mechanical strain regulates osteoblast proliferation through integrin-mediated ERK activation.
abstract: 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.
authors.affiliation: Institute of Medical Equipment, Academy of Military Medical Science, Tianjin, China.
authors.forename: Yu-xian
authors.initials: YX
authors.lastname: Yan
authors.forename: Yuan-wei
authors.initials: YW
authors.lastname: Gong
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruixin
authors.initials: R
authors.lastname: Li
authors.forename: Xi-zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D020869:Gene Expression Profiling; D039641:Integrin beta Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical
chemical_list: D005419:Flavonoids; D039641:Integrin beta Chains; D019012:Integrin beta1; D034741:RNA, Small Interfering; C084344:integrin beta5; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one