Complementary modulation of BMP signaling improves bone healing efficiency
- Authors
- Fan, Jiabing; Zhang, Xiao; Kang, Minjee; Kim, Lauren; Lee, Chung-Sung; Hadaya, Danny; Aghaloo, Tara L.; Lee, Min
- Issue Date
- Nov-2023
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Noggin; Trb3; BMP signaling; Sterosome; Bone repair
- Citation
- BIOMATERIALS, v.302
- Journal Title
- BIOMATERIALS
- Volume
- 302
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/25889
- DOI
- 10.1016/j.biomaterials.2023.122335
- ISSN
- 0142-9612
1878-5905
- Abstract
- 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 nonphospholipid 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.
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Collections - College of Medical Sciences > Department of Pharmaceutical Engineering > 1. Journal Articles
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