Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

“Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates.  We wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

“IGF-1 and MGF are up-regulated in exercised and damaged skeletal muscle, probably inducing muscle growth and hypertrophy. MGF has been shown to stimulate proliferation and suppress differentiation, while IGF-1 also supported differentiation”

“Cyclic stretching of osteoblasts enhanced cell proliferation and induced expression of Mgf on the mRNA level. MGF has been observed to inhibit osteoblast differentiation and mineralization in osteoblast cell culture medium”

“Injecting MGF into [a] bone defect gap for 5 consecutive days resulted in accelerated bone healing”

“Comparison of mRNA expression revealed that the Mgf fraction of total Igf1 ratios varied between the tissues examined ranging from 8% in muscle to 31% in Ranvier’s groove “<-So MGF and IGF-1 correlates between muscle, bone, and cartilage tissue.

“Igf1 and Mgf expressions were lower in the proliferative zone than in the resting and hypertrophic zones”

“[No] statistically significant effects of the MGF peptides on the proliferation of monolayer growth plate chondrocytes in concentrations ranging from 0.1 to 500 ng/ml. Differences between concentrations could be detected when growth plate explants were treated with IGF-1 alone”

“In contrast to mature IGF-1, MGF has been reported to activate ERK1/2 without influencing Akt phosphorylation”

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