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Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein

1
Department of Prosthodontics, College of Dentistry, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, Korea
2
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, Korea
3
Research Institute for Precision Immuno-medicine, Good T Cells Incorporated, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, Korea
*
Author to whom correspondence should be addressed.
Academic Editors: Xiangxiang Zeng, Alfonso Rodríguez-Patón and Quan Zou
Molecules 2019, 24(4), 760; https://doi.org/10.3390/molecules24040760
Received: 8 January 2019 / Revised: 15 February 2019 / Accepted: 18 February 2019 / Published: 20 February 2019
(This article belongs to the Special Issue Molecular Computing and Bioinformatics)
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PDF [2418 KB, uploaded 20 February 2019]
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Abstract

Patients with uncontrolled diabetes are susceptible to implant failure due to impaired bone metabolism. Hypoxia-inducible factor 1α (HIF-1α), a transcription factor that is up-regulated in response to reduced oxygen during bone repair, is known to mediate angiogenesis and osteogenesis. However, its function is inhibited under hyperglycemic conditions in diabetic patients. This study thus evaluates the effects of exogenous HIF-1α on bone formation around implants by applying HIF-1α to diabetic mice and normal mice via a protein transduction domain (PTD)-mediated DNA delivery system. Implants were placed in the both femurs of diabetic and normal mice. HIF-1α and placebo gels were injected to implant sites of the right and left femurs, respectively. We found that bone-to-implant contact (BIC) and bone volume (BV) were significantly greater in the HIF-1α treated group than placebo in diabetic mice (p < 0.05). Bioinformatic analysis showed that diabetic mice had 216 differentially expressed genes (DEGs) and 21 target genes. Among the target genes, NOS2, GPNMB, CCL2, CCL5, CXCL16, and TRIM63 were found to be associated with bone formation. Based on these results, we conclude that local administration of HIF-1α via PTD may boost bone formation around the implant and induce gene expression more favorable to bone formation in diabetic mice. View Full-Text
Keywords: diabetes mellitus; hypoxia-inducible factor-1α; angiogenesis; bone formation; osteogenesis; protein transduction domain diabetes mellitus; hypoxia-inducible factor-1α; angiogenesis; bone formation; osteogenesis; protein transduction domain
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Oh, S.-M.; Shin, J.-S.; Kim, I.-K.; Kim, J.-H.; Moon, J.-S.; Lee, S.-K.; Lee, J.-H. Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein. Molecules 2019, 24, 760.

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