3163 - Low Dose Radiation Enhances Anti-Inflammatory Effect of Creatine and Overcomes Type 1 Diabetes-Induced Suppression of Osteogenesis and Angiogenesis

05:00pm - 06:00pm PT

Hall F

Screen: 15

POSTER

Presenter(s)

Geng Xiang, - Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi

G. Xiang, and L. Zhao; Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, xi an, shan xi, China

Purpose/Objective(s):

Type 1 diabetes mellitus is a chronic metabolic disease with a pro-inflammatory microenvironment, causing poor vascularization and bone regeneration. Due to the lack of effective therapy and one-sided focus on the osteogenesis and angiogenesis stimulation, the treatment of diabetic osteopathy remains challenging and complex. The aim of the present study was to explore the effects of creatine and low dose radiation on osteogenesis and angiogenesis in the bones of diabetic mice.

Materials/Methods:

T1DM was induced in mice by streptozotocin (STZ) injection. Diabetic mice were irradiated with whole-body X-rays at a single dose of 25 mGy, 50 mGy, 75 mGy, 100 mGy and then sacrificed. Body weight, blood glucose level, and TNF-a, iNOS, SOD1 expression were measured to determine the optimal radiation dose. Creatine and low-dose radiation were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated.

Results:

In vivo experiments showed that low-dose radiation had no impact on the body weights or blood glucose levels of the mice in different groups but low-dose radiation of 50 mGy could significantly decrease expression of pro-inflammatory cytokines and increase the expression of SOD1. Detection of macrophage polarity in peripheral blood samples showed that creatine supplementation inhibited M1 macrophage while promoting M2 polarization. Further results showed that low-dose radiation could increase the level of creatine in macrophages. Low-dose radiation and exogenous creatine could significantly promote the polarization of M2 macrophages in diabetic conditon and promote osteogenesis and angiogenesis compared to low-dose radiation alone or creatine supplementation alone.

Conclusion:

Our finding innovatively revealed that low-dose radiation of 50 mGy combined with creatine promoted osteogenesis and angiogenesis by triggering M2 polarization of macrophages, which provided a new perspective for immune mechanism study in the treatment of diabetic osteopathy.