Effect of cyclic uni-axial strain on IGF-I Ea and MGF gene expression by osteoblasts and osteocytes

96 ABSTRACT IGF-I is a key regulatory growth factor in the adaptation of bone mass and structure to mechanical loading. Two isoforms of IGF-I, IGF-I Ea and MGF are expressed by osteocytes and osteoblasts. The expression of MGF by osteoblasts is increased in response to mechanical loading by cyclic uni-axial strain (CS). It is however unknown whether IGF-I Ea expression by osteoblasts is affected by CS, and whether CS alters the expression of MGF and IGF-I EA by osteocytes. Therefore, we aimed to investigate whether CS affects the expression of IGF-I Ea and MGF by MC3T3-E1 osteoblasts and MLO-Y4 osteocytes, and whether these effects are different in osteoblasts compared to osteocytes. MC3T3-E1 osteoblasts and MLO-Y4 osteocytes were subjected to CS (3Hz, 5% deformation) for 1 h. IGF-I Ea and MGF mRNA expression levels in osteoblasts and osteocytes were measured from RNA samples which were collected at 1h CS, and at 1, 3, 6, and 24 h post-CS. Basal IGF-I Ea and MGF gene expression levels were 300-fold higher in MC3T3-E1 osteoblasts compared to MLO-Y4 osteocytes. CS stimulated both IGF-I Ea and MGF mRNA expression levels in osteoblasts, but only directly after 1h CS. In osteocytes CS also increased MGF gene expression at 1 h CS, but CS did not affect IGF-I Ea mRNA expression levels at any time point measured. In conclusion, CS increases IGF-I Ea and MGF mRNA gene expression levels by osteoblasts, whereas in osteocytes, only MGF mRNA levels were increased in response to CS. The lack of increase in IGF-I Ea gene expression by osteocytes in response to CS seems curious since mechanical loading induced IGF-I gene expression is important for bone maintenance in vivo. This may indicate that for osteocytes the increase in IGF-I Ea expression is likely due to fluid flow in the canaliculi rather than tensile strain.