Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein
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 osteogene...
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| Format: | Article |
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MDPI AG
2019-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/4/760 |
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| author | Sang-Min Oh Jin-Su Shin Il-Koo Kim Jung-Ho Kim Jae-Seung Moon Sang-Kyou Lee Jae-Hoon Lee |
| author_facet | Sang-Min Oh Jin-Su Shin Il-Koo Kim Jung-Ho Kim Jae-Seung Moon Sang-Kyou Lee Jae-Hoon Lee |
| author_sort | Sang-Min Oh |
| collection | DOAJ |
| description | 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 (<i>p</i> < 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. |
| first_indexed | 2024-12-19T19:36:17Z |
| format | Article |
| id | doaj.art-5eeec780c633436d8c526f7244f047a9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-19T19:36:17Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5eeec780c633436d8c526f7244f047a92022-12-21T20:08:26ZengMDPI AGMolecules1420-30492019-02-0124476010.3390/molecules24040760molecules24040760Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding ProteinSang-Min Oh0Jin-Su Shin1Il-Koo Kim2Jung-Ho Kim3Jae-Seung Moon4Sang-Kyou Lee5Jae-Hoon Lee6Department of Prosthodontics, College of Dentistry, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaResearch Institute for Precision Immuno-medicine, Good T Cells Incorporated, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaDepartment of Prosthodontics, College of Dentistry, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 03722, KoreaPatients 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 (<i>p</i> < 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.https://www.mdpi.com/1420-3049/24/4/760diabetes mellitushypoxia-inducible factor-1αangiogenesisbone formationosteogenesisprotein transduction domain |
| spellingShingle | Sang-Min Oh Jin-Su Shin Il-Koo Kim Jung-Ho Kim Jae-Seung Moon Sang-Kyou Lee Jae-Hoon Lee Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein Molecules diabetes mellitus hypoxia-inducible factor-1α angiogenesis bone formation osteogenesis protein transduction domain |
| title | Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein |
| title_full | Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein |
| title_fullStr | Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein |
| title_full_unstemmed | Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein |
| title_short | Therapeutic Effects of HIF-1α on Bone Formation around Implants in Diabetic Mice Using Cell-Penetrating DNA-Binding Protein |
| title_sort | therapeutic effects of hif 1α on bone formation around implants in diabetic mice using cell penetrating dna binding protein |
| topic | diabetes mellitus hypoxia-inducible factor-1α angiogenesis bone formation osteogenesis protein transduction domain |
| url | https://www.mdpi.com/1420-3049/24/4/760 |
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