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Efficient in vitro delivery of Noggin siRNA enhances osteoblastogenesis.

Authors
  • Ghadakzadeh, S1, 2, 3
  • Hamdy, R C1, 2
  • Tabrizian, M3, 4
  • 1 Experimental Surgery, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Canada. , (Canada)
  • 2 Division of Orthopaedic Surgery, Shriners Hospital for Children, McGill University, Montreal, Canada. , (Canada)
  • 3 Department of Biomedical Engineering, McGill University, Montreal, Canada. , (Canada)
  • 4 Faculty of Dentistry, McGill University, Montreal, Canada. , (Canada)
Type
Published Article
Journal
Heliyon
Publisher
Elsevier
Publication Date
Nov 01, 2017
Volume
3
Issue
11
Identifiers
DOI: 10.1016/j.heliyon.2017.e00450
PMID: 29167826
Source
Medline
Keywords
License
Unknown

Abstract

Several types of serious bone defects would not heal without invasive clinical intervention. One approach to such defects is to enhance the capacity of bone-formation cells. Exogenous bone morphogenetic proteins (BMP) have been utilized to positively regulate matrix mineralization and osteoblastogenesis, however, numerous adverse effects are associated with this approach. Noggin, a potent antagonist of BMPs, is an ideal candidate to target and decrease the need for supraphysiological doses of BMPs. In the current research we report a novel siRNA-mediated gene knock-down strategy to down-regulate Noggin. We utilized a lipid nanoparticle (LNP) delivery strategy in pre-osteoblastic rat cells. In vitro LNP-siRNA treatment caused inconsequential cell toxicity and transfection was achieved in over 85% of cells. Noggin siRNA treatment successfully down-regulated cellular Noggin protein levels and enhanced BMP signal activity which in turn resulted in significantly increased osteoblast differentiation and extracellular matrix mineralization evidenced by histological assessments. Gene expression analysis showed that targeting Noggin specifically in bone cells would not lead to a compensatory effect from other BMP negative regulators such as Gremlin and Chordin. The results from this study support the notion that novel therapeutics targeting Noggin have the clinically relevant potential to enhance bone formation without the need for toxic doses of exogenous BMPs. Such treatments will undeniably provide safe and economical treatments for individuals whose poor bone repair results in permanent morbidity and disability.

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