Inhibition of human osteoblast marker gene expression by retinoids is mediated in part by insulin-like growth factor binding protein-6

Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society
T YanD D Strong

Abstract

All-trans -retinoic acid (atRA) inhibits osteoblast marker gene expression and markedly increases expression of insulin-like growth factor binding protein-6 (IGFBP-6) in human osteoblasts. The possibility that IGFBP-6 inhibits the osteoblast phenotype and also mediates the inhibitory effect of atRA on osteoblast marker gene expression was explored using an antisense approach. Stable human osteoblast-like osteosarcoma SaOS-2 cells were prepared that expressed antisense IGFBP-6 RNA under basal and atRA-stimulated conditions. The functional expression of IGFBP-6 antisense RNA was confirmed by measuring IGFBP-6 mRNA by Northern analysis or by measuring IGFBP-6 protein in the conditioned media (CM) by radioimmunoassay. Antisense clones produced less mRNA and had less IGFBP-6 protein in the CM than controls. IGFBP-6 protein levels in the CM were inversely correlated with alkaline phosphatase (ALP) activity, whereas IGFBP-3 and IGFBP-4 protein levels were not. We reasoned that atRA would have little or no effect on ALP activity in IGFBP-6 antisense clones if atRA mediated its inhibitory effects by recruiting IGFBP-6. In the majority of IGFBP-6 antisense clones with the lowest IGFBP-6 mRNA and CM protein levels and only modest changes ...Continue Reading

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Citations

Nov 19, 2004·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Kristen E GovoniSubburaman Mohan
Mar 3, 2006·Journal of Gastroenterology and Hepatology·Junming GuoWeihong Zhao
May 10, 2015·Journal of Bone and Mineral Metabolism·Timur A YorganThorsten Schinke
Nov 3, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Leon A Bach
Dec 4, 2002·Journal of Cellular Biochemistry·Igor B Roninson, Milos Dokmanovic
Jan 6, 2007·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Martha H Meyer, Ralph A Meyer
Nov 7, 2012·Clinical Science·Leon A BachZhiyong Yang
Jun 19, 2013·Biochemical and Biophysical Research Communications·Jianwei LiGang Wang
Mar 27, 2015·Journal of Cell Communication and Signaling·Leon A Bach

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