Abstract
To elucidate the role of endogenous transforming growth factor (TGF)-β2 on human osteoblast cell, antisense phosphorothioate oligonucleotides (S-ODNs) complementary to regions in mRNA of TGF-β2 were synthesized and examined their effects on TGF-β2 production and cell proliferation in a human osteoblast cell line ROS 17/2. Antisense S-ODNs were designated for three different target regions in the mRNA of TGF-β2. Among several antisense S-ODN analyzed, an oligonucleotide (AS-11) complementary to the translation initiation site of mRNA of TGF-β2 demonstrated a selective and strong inhibitory effect on TGF-β2 production in osteoblast cells. Other antisense S-ODNs which were designated for other regions in mRNA of TGF-β2 and one- or three-base mismatched analogs of AS-11 showed little or much less antisense activities than AS-11. Therefore, the most effective target site in mRNA of TGF-β2 is at the initiation codon region. The antisense effects of AS-11 were observed without reduction of levels of mRNA of TGF-β2. Furthermore, the inhibition of TGF-β2 expression by antisense S-ODN appeared to enhance cell proliferation, demonstrating the growth inhibitory effect of autocrine TGF-β2 in osteoblast cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2331-2337 |
| Number of pages | 7 |
| Journal | European Journal of Biochemistry |
| Volume | 268 |
| Issue number | 8 |
| DOIs | |
| State | Published - 2001 |
Keywords
- Antisense oligonucleotides
- Osteoblast cell
- TGF-β2 expression
ASJC Scopus subject areas
- Biochemistry