Insulinlike growth factor 1 regulates mRNA levels of osteonectin and pro-α1(I)-collagen in clonal preosteoblastic calvarial cells

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Abstract
A nontransformed rat clonal cell line (UMR‐201) with phenotypic characteristics of osteoblastic precursor cells was found to respond to insulinlike growth factor 1 (IGF‐1) by increased osteonectin and pro‐α1 (1)‐collagen mRNA expression. Cells were treated for 24 h with insulin, growth hormone, or IGF‐1 to study the regulation of messenger RNA for osteonectin and pro‐α1(I)‐collagen using Northern blot hybridization. UMR‐201 cells possess specific high‐affinity receptors for growth hormone, although there were no significant effects of growth hormone (10−9‐10−7 M) or insulin (10−9‐10−6 M) on mRNA species for osteonectin or pro‐α(I)‐collagen. However, IGF‐1 increased both mRNA species from a concentration of 10−9 M. The effect on osteonectin mRNA expression was likely due to increased transcription; when 5′ flanking osteonectin (ON) genomic fragments were linked to the bacterial reporter gene chloramphenicol acetyltransferase (CAT) and introduced by transfection into UMR‐201 cells, the transcriptional activity of the ON‐CAT construct was increased 235 and 270% by 10−8 and 10−7 M IGF‐1, respectively. In contrast, growth hormone did not change the transcriptional activity of the ON‐CAT construct. In confirmation of other work, transforming growth factor β (TGF‐β, 0.1‐2.5 ng/ml) increased mRNA for osteonectin and pro‐α1(I)‐collagen in a dose‐dependent manner. Transforming growth factor α (TGF‐α) at 0.1‐10 ng/ml had no consistent effects in repeated experiments on osteonectin and pro‐α1(I)‐collagen mRNA. The positive stimulatory effect of both IGF‐1 and TGF‐β provides insights on the regulation of bone matrix proteins and suggests a major role of these growth factors in the remodeling process of bone.
Funding Information
  • Swiss Foundation
  • National Health and Medicine Research Council of Australia