Journal article
A Comparative Study of the Bone Regenerative Effect of Chemically Modified RNA Encoding BMP-2 or BMP-9
The AAPS journal, Vol.19(2), pp.438-446
03/2017
DOI: 10.1208/s12248-016-0034-8
PMCID: PMC5712477
PMID: 28074350
Abstract
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2. Polyethylenimine (PEI) was used as a vector to increase in vitro transfection efficacy. Complexes of PEI-cmRNA (encoding BMP-2 or BMP-9) were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficacy in vitro using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these complexes was determined by evaluating the expression of bone-specific genes as well as through the detection of bone matrix deposition. It was found that alkaline phosphatase (ALP) expression 3 days post transfection in the group treated with BMP-9-cmRNA was significantly higher than that in the group that received BMP-2-cmRNA treatment. Alizarin red staining and atomic absorption spectroscopy demonstrated enhanced osteogenic differentiation as evidenced by increased bone matrix production by the BMSCs treated with BMP-9-cmRNA when compared to cells treated with BMP-2-cmRNA. In vivo studies showed increased bone formation in calvarial defects treated with the BMP-9-cmRNA and BMP-2-cmRNA collagen scaffolds when compared to empty defects. The connectivity density of the regenerated bone was higher (2-fold-higher) in the group that received BMP-9-cmRNA compared to BMP-2-cmRNA. Together, these findings suggest that cmRNA-activated matrix encoding osteogenic molecules can provide a powerful strategy for bone regeneration with significant clinical translational potential.
Details
- Title: Subtitle
- A Comparative Study of the Bone Regenerative Effect of Chemically Modified RNA Encoding BMP-2 or BMP-9
- Creators
- Behnoush Khorsand - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, Iowa, USASatheesh Elangovan - Department of Periodontics, University of Iowa College of Dentistry, Iowa City, Iowa, USA. satheeshelangovan@uiowa.eduLiu Hong - Department of Prosthodontics, University of Iowa College of Dentistry, Iowa City, Iowa, USAAlexander Dewerth - Department of Pediatrics (Section I), Translational Genomics and Gene Therapy, University of Tübingen, Wilhelmstr. 27, 72074, Tübingen, GermanyMichael S D Kormann - Department of Pediatrics (Section I), Translational Genomics and Gene Therapy, University of Tübingen, Wilhelmstr. 27, 72074, Tübingen, GermanyAliasger K Salem - Department of Periodontics, University of Iowa College of Dentistry, Iowa City, Iowa, USA. aliasger-salem@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The AAPS journal, Vol.19(2), pp.438-446
- DOI
- 10.1208/s12248-016-0034-8
- PMID
- 28074350
- PMCID
- PMC5712477
- NLM abbreviation
- AAPS J
- ISSN
- 1550-7416
- eISSN
- 1550-7416
- Publisher
- United States
- Grant note
- P30 CA086862 / NCI NIH HHS R21 DE024206 / NIDCR NIH HHS
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Prosthodontics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Periodontics
- Record Identifier
- 9983985834002771
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