Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation - PubMed (original) (raw)

. 2008 Jun;42(6):1092-101.

doi: 10.1016/j.bone.2008.02.011. Epub 2008 Feb 29.

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Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation

Céline Faure et al. Bone. 2008 Jun.

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Abstract

Since VEGF-A is involved in mechanically induced bone gain and because vegf exists under 6 isoforms exerting various biological effects, we studied vegf isoform expression and VEGF protein production in osteoblastic cells (rat Ros17/2.8 and human osteoblasts) submitted to 4 mechanical regimens. Mechanical regimens (1% stretch deformation) were designed with a fixed number of cycles (450) delivered at various frequencies (0.05 to 5 Hz). We found a negative correlation (R(2)=0.76, p<0.0001) between production of soluble VEGF and mechanical stretch frequency and a positive correlation (R(2)=0.99, p<0.0001) between production of matrix-bound VEGF and mechanical stretch frequency. mRNA expressions of soluble VEGF isoforms (121, 165) were specifically expressed under low frequency while matrix-bound VEGF isoforms (206, 189, 165, 145) were specifically expressed under high frequency in human osteoblasts. As f-actin stress fiber formation was significantly increased selectively in high frequency conditions, we disrupted actin fibers in Ros17/2.8 and found that immobilisation of VEGF was abolished. Conversely, Jasplakinolide treatment which increases stress fiber formation was able to mimic high frequency stretch-induced immobilisation of VEGF. Thus, we speculate that the stretch-induced increase in cell tension is responsible for matrix-bound vegf isoform production. Mechanically induced selection of soluble or matrix-bound VEGF production may modify osteoblast and endothelial cell crosstalk crucial during osteogenesis and fracture healing.

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