TGF-β1 RNA Interference in Mouse Primary Dura Cell Culture: Downstream Effects on TGF Receptors, FGF-2, and FGF-R1 mRNA Levels

Abstract

These results indicate that TGF-beta1 siRNA has the potential to alter the murine dura cytokines responsible for suture fusion in vitro. Manipulating underlying cranial suture biology with siRNA technology may ultimately allow control over suture fusion. This intervention may ultimately function as an effective adjunct to surgical intervention for craniosynostosis.

Long-Term Gene-Silencing Effects of siRNA Introduced by Single-Cell Electroporation into Postmitotic CNS Neurons

“…Song et al (2003) showed that sufficient siRNA effects continue at least for 10 days in hepatocytes probably because hepatocytes are mostly nondividing [17]. Also in endothelial [18], dura [19] and skin [20] cells, siRNA effects continued at least for 7-10 days. The present study clearly showed that siRNA effects continue for a longer period in postmitotic neurons, at least under our experimental conditions.…”

Signaling mechanisms implicated in cranial sutures pathophysiology: Craniosynostosis

“…RNA interference has been used by recent studies, both in vitro [118] and in vivo [101]. Gosain and colleagues used endogenous anti-TGF-β1 small interfering RNA to target and knockdown TGF-β1 mRNA transcripts, which are expressed during cranial suture formation and may affect FGFR signaling.…”

“…Ultimately, a decrease in mRNA levels of FGF2 and FGFR1, as well as a successful knockdown of TGF-β1, was observed. TGF-β1 siRNA has the potential to change signaling in the mouse dura, which is responsible for suture fusion in vitro [118]. In vivo studies were also performed by using small hairpin RNA to target the mutant FGFR2 with the S252W mutation transcripts in the Apert syndrome mouse model.…”

Craniosynostosis

“…81 More recently, suppression of TGF-β1 through RNA interference in mouse primary dura cell culture has been shown to downregulate expression of FGF-2 and FGFR-1. 82,83 This again raises the exciting prospect of using siRNAs to suppress genes involved in promoting suture fusion. But as mentioned above, an efficient and safe means to deliver siRNA constructs must be first developed to achieve clinical efficacy and ongoing studies are evaluating a variety of synthetic vehicles including nanoparticles, liposomes, and other lipid-like materials.…”