Alternative splicing and expression of the insulin-like growth factor (IGF-1) gene in osteoblasts under mechanical stretch
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Insulin-like growth factor 1 (IGF-1) promotes osteoblasts differentiation and bone formation, and its expression is induced by mechanical stretch, thus IGF-1 has been considered an effector molecule that links mechanical stimulation and local tissue responses. In this study, a mechanical stretching device was designed to apply physiological level static or cyclic stretching stimulation to osteoblasts. Different isoforms of IGF-1 mRNA were amplified by RT-PCR from the cells using respective primers and these amplified products were sequenced. An isoform of IGF-1 splicing product was found to be selectively produced by osteoblasts under stretching stimulation. This IGF-1 isoform had identical sequence with the mechano growth factor (MGF) which was originally identified in muscle cells. Regulations of the expression of the liver-type IGF (L.IGF-1) and MGF in osteoblasts under stretch stimulation were further studied using semi-quantitative RT-PCR. Stretch stimulation was found to promot the expression of IGF-1 (L.IGF-1 and MGF), and for both isoforms expression was more effectively stimulated by cyclic stretch than static stretch. MGF was detected only in osteoblasts subjected to mechanical stretch, suggesting MGF was a stretch sensitive growth factor. Expression of MGF peaked earlier than that of L.IGF-1, which was similar to their regulation in muscle and suggested similar roles of MGF and L.IGF-1 in bone as in muscle cells. The functions of MGF and L.IGF-1 in osteoblasts shall be established by further experimental studies.
Keywordsinsulin-like growth factor-1 (IGF-1) mechano growth factor (MGF) alternative splice osteoblasts stretching
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