In the current study, we determined the effects of IGF-1 receptor haploinsufficiency on osteoblast differentiation and bone formation throughout the lifespan. Bone mineral density was significantly decreased in femurs of male and female Igf1r+/- mice compared with wild-type mice.mRNA expression of osteoblast differentiation markers was significantly decreased in femurs and calvariae from Igf1r+/- mice compared with cells from wild-type mice. Bone morphogenetic protein-7-induced ectopic bone in Igf1r+/- mice was significantly smaller with fewer osteoblasts but more lipid droplets and had reduced expression of osteoblast differentiation markers compared with wild-type mice. In bone marrow cells from middle-aged and old wild-type and Igf1r+/- male mice, palmitate inhibited osteoblast markers expression. In cells from young wild-type male mice, palmitate did not inhibit marker expression, but in cells from young male Igf1r+/- mice, palmitate inhibited bone sialoprotein and osterix but not osteocalcin or type I collagen (TIC). In female wild-type mice, palmitate inhibited osteoblast markers expression in cells from young, middleaged, andold mice except TIC in cells from middle-aged mice. Palmitate inhibitedbonesialoprotein expression in cells from middle-aged and old female Igf1r+/- mice and osteocalcin, osterix, and TIC expression in young and middle-aged female Igf1r+/- mice but stimulated expression in cells from old female Igf1r+/- mice. We conclude that IGF-1 receptor haploinsufficiency results in a prolipid accrual phenotype in bone in association with inhibition of growth factor-induced osteoblast differentiation, a situation which may phenocopy age-related decreases in bone formation.
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