Journal
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Volume 11, Issue 11, Pages 3068-3077Publisher
WILEY
DOI: 10.1002/term.2208
Keywords
adipose-derived stem cells; baculovirus; calvarial bone defect; miR-148b; BMP-2; Cre/loxP; noggin
Categories
Funding
- National Tsing Hua University (Toward World-Class University) [104N2050E1]
- National Tsing Hua University (NTHU-CGMH Joint Research Programme) [CMRPG3D0591, 103N2758E1]
- CGMH Intramural Project [CRRPG3E0172, CMRPG3E0441, CMRPG3E0061]
- Ministry of Science and Technology, Taiwan [MOST 104-2221-E-007-088-MY3, MOST 101-2628-E-007-009-MY3, 101-2923-E-007-002-MY3]
Ask authors/readers for more resources
Repairing large calvarial bone defects remains a challenging task. Previously, it was discovered that that miR-148b, when acting in concert with bone morphogenetic protein 2 (BMP-2), enhanced the osteogenesis of human adipose-derived stem cells (hASCs) and improved calvarial bone healing in nude mice. However, the molecular target of miR-148b remained elusive. Here it is revealed that miR-148b directly targets NOG, whose gene product (noggin) is an antagonist to BMPs and negatively regulates BMP-induced osteogenic differentiation and bone formation. A new Cre/loxP-based baculovirus system was employed to drive prolonged BMP-2 and miR-148b overexpression in hASCs, wherein the BMP-2 overexpression induced noggin expression but the concurrent miR-148b expression downregulated noggin, thus relieving the negative regulatory loop and ameliorating hASC osteogenesis without hindering hASC proliferation or triggering appreciable cytotoxicity. Implantation of the engineered hASCs coexpressing BMP-2 and miR-148b into nude mice enabled substantial repair of critical-size calvarial bone defects (4 mm diameter) at 12 weeks post-transplantation, filling 83% of the defect area, 75% of bone volume and restoring the bone density to 89% of the original bone density. Such superior healing effects indicate the potential of the Cre/loxP-based baculovirus-mediated BMP-2/miR-148b expression for calvarial bone repair. Copyright (c) 2016 John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available