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Post-transcriptional Regulation in Osteoblasts using Localized Delivery of miR-29a Inhibitor from Nanofibers to Enhance Extracellular Matrix Deposition.
MedLine Citation:
PMID:  24816265     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
MicroRNAs are important post-transcriptional regulators of skeletal biology, and miRNA-based therapeutics have the potential to aid bone repair. However, efficient tools to deliver miRNA mimics or inhibitors to specific target tissues are limited. Polymeric nanofibers closely mimic natural extracellular matrix morphology, and are attractive candidates to support delivery of cells and bone-anabolic reagents. We hypothesized that gelatin nanofibers could be used for the localized transient delivery of miRNA-based therapeutics, using miR-29a inhibitor as a prototype to increase extracellular matrix (ECM) deposition. miR-29 family members are negative regulators of ECM synthesis, targeting the mRNAs of selected collagens and osteonectin/SPARC. Inhibiting miR-29 activity may therefore, increase extracellular matrix production by cells. miR-29a inhibitor loaded gelatin nanofibers, prepared by electrospinning, demonstrated continuous release of miRNA inhibitor over 72 hours. Pre-osteoblastic murine MC3T3-E1 cell line seeded on miR-29a inhibitor loaded nanofibers synthesized more osteonectin, indicating efficient inhibitor delivery. These cells also displayed increased Igf1 and Tgfb1 mRNA. Moreover, primary bone marrow stromal cells from transgenic pOBCol3.6cyan reporter mice, grown on miR-29a inhibitor scaffolds, displayed increased col3.6 cyan expression as well as collagen production. This study demonstrated that ECM mimicking nanostructured scaffolds, in conjunction with bioactive miRNA-based therapeutics, may serve as a novel platform for developing biologically active localized cell delivery systems.
Authors:
Eric N James; Anne M Delany; Lakshmi S Nair
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-7
Journal Detail:
Title:  Acta biomaterialia     Volume:  -     ISSN:  1878-7568     ISO Abbreviation:  Acta Biomater     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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