| First Author | Xiong Y | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 494 |
| Issue | 3-4 | Pages | 626-633 |
| PubMed ID | 29080745 | Mgi Jnum | J:251420 |
| Mgi Id | MGI:6103802 | Doi | 10.1016/j.bbrc.2017.10.024 |
| Citation | Xiong Y, et al. (2017) 1alpha,25-Dihydroxyvitamin D3 increases implant osseointegration in diabetic mice partly through FoxO1 inactivation in osteoblasts. Biochem Biophys Res Commun 494(3-4):626-633 |
| abstractText | Oral implant osseointegration is delayed by hyperglycemia-generated oxidative stress (OS). Forkhead transcription factor 1 (FoxO1) is known to be viewed as a sensor to OS since reactive oxide species like H2O2 regulates its activity. We previously demonstrated that 1,25(OH)2D3 favored glucose homeostasis and implant osseointegration in diabetic rats. In this study, we investigated the role of FoxO1OB in the regulation process of 1,25(OH)2D3 on glycometabolism and bone metabolism. We show herein that, with the treatment of 1,25(OH)2D3, mice lacking FoxO1 in osteoblasts (FoxO1OB(-/-)) exhibited decreased serum glucose that was gradually elevated in untreated diabetic mice. An optimal increase of bone mass and bone-implant contact (BIC) was observed in 1,25(OH)2D3 treated FoxO1OB(-/-) mice after 2-month healing. Surprisingly, FoxO1OB(-/-) mice without 1,25(OH)2D3 treatment also showed an improvement on bone formation and BIC. Same effect could be found in the expression of bone-related markers Runx2, Osterix and BSP, which elevated in 1,25(OH)2D3 treated FoxO1OB(-/-) mice as compared to untreated WT mice. In addition, in vitro study showed that high glucose induced FoxO1 nuclear localization while the effect was ameliorated by 1,25(OH)2D3 treatment. These results suggest that FoxO1OB might be involved in the regulation of 1,25(OH)2D3 on glucose homeostasis and bone formation, and that FoxO1OB might act as a key modulator of the capacity of the skeleton regulating metabolic homeostasis. Our study also provides a new idea that a combination of systemic 1,25(OH)2D3 and local FoxO1 inhibitor may be a new approach to enhance implant osseointegration. |
