Complementary modulation of BMP signaling improves bone healing efficiency

The bone morphogenetic protein (BMP) signaling pathway plays a crucial role in bone development and regeneration. While BMP-2 is widely used as an alternative to autograft, its clinical application has raised concerns about adverse side effects and deteriorated bone quality. Therefore, there is a ne...

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Bibliographic Details
Published in:Biomaterials 2023-11, Vol.302, p.122335-122335, Article 122335
Main Authors: Fan, Jiabing, Zhang, Xiao, Kang, Minjee, Lee, Chung-Sung, Kim, Lauren, Hadaya, Danny, Aghaloo, Tara L., Lee, Min
Format: Article
Language:English
Subjects:
BMP signaling
Bone Morphogenetic Protein 2 - metabolism
Bone Morphogenetic Protein 2 - pharmacology
Bone Regeneration
Bone repair
Cell Differentiation
Mesenchymal Stem Cells
Noggin
Osteogenesis
Signal Transduction
Sterosome
Trb3
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Summary:The bone morphogenetic protein (BMP) signaling pathway plays a crucial role in bone development and regeneration. While BMP-2 is widely used as an alternative to autograft, its clinical application has raised concerns about adverse side effects and deteriorated bone quality. Therefore, there is a need to develop more sophisticated approaches to regulate BMP signaling and promote bone regeneration. Here, we present a novel complementary strategy that targets both BMP antagonist noggin and agonist Trb3 to enhance bone defect repair without the application of exogenous BMP-2. In vitro studies showed that overexpression of Trb3 with simultaneous noggin suppression significantly promotes osteogenic differentiation of mesenchymal stem cells. This was accompanied by increased BMP/Smad signaling. We also developed sterosome nanocarriers, a non-phospholipid liposomal system, to achieve non-viral mediated noggin suppression and Trb3 overexpression. The gene-loaded sterosomes were integrated onto an apatite-coated polymer scaffold for in vivo calvarial defect implantation, resulting in robust bone healing compared to BMP-2 treatments. Our work provides a promising alternative for high-quality bone formation by regulating expression of BMP agonists and antagonists.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2023.122335