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Mechanical loading boosts expression of VEGF and HGF in osteocytes


Mechanical loading is known to have a similar anabolic and metabolic effect on bone to regular physical activity, but the molecular events underlying this response have not been investigated. In this study, MLO-Y4 osteocytes were subjected to mechanical loading using pulses of fluid, and the effect on the expression of various key genes was monitored.

Normally, MLO-Y4 osteocytes express the mRNA of genes encoding vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor-I isoforms (IGF-I Ea) and mechano-growth factor (MGF) but do not express myostatin mRNA. Mechanical loading increased expression of VEGF by 1.8 to 2.5 times, and increased the levels of VEGF protein within the cells 2.0- to 2.9-fold. The mRNA levels of HGF decreased 1.5-fold but expression of the HGF protein rose by 2.3 times baseline. The levels of IGF-I Ea and MGF mRNA did increase slightly under a high physiological shear rate but levels of these proteins remained very low.

The authors conclude that osteocytes respond to mechanical loading by producing more VEGF and HGF, which suggests that these proteins play previously unrealized roles in bone remodeling mediated by loading.

Editor's comment: It remains possible that increases in IGF-I Ea and MGF in nearby muscle cells supply large enough quantities of these proteins to osteocytes to enhance bone response to muscle loading; further analysis of this cross-talk may reveal new therapeutic targets for osteoporosis and sarcopenia.

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