Inhibition of adipogenesis is involved in the protective effects of 1,25-dihydroxy vitamin D3 on the radiation-injured bone marrow microenvironment in mice
2017
Zhou, Z. ((Jinan University, Guangzhou, Guangdong Province (China). Medical College, Institute of Hematology), (Jinan University, Guangzhou, Guangdong Province (China). Key Laboratory for Regenerative Medicine of the Ministry of Education), (Jinan University, Guangzhou, Guangdong Province (China). Joint Laboratory for Regenerative Medicine (JUN-CUHK))) | Chen, X.Y. | Zhu, A.Z. | Liu, C.C. | Zhu, J.C. | Liu, G.X.
To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on the bone marrow microenvironment in mice after irradiation and the underlying molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly divided into a normal group, an irradiation (IR) group and an irradiation+1,25-(OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy sup(60)Cogamma rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 microg/kg) was administered once per day from 2 d before to 8 d after irradiation. Mice in the IR group were treated with the same dose of gamma rays and an equal volume of DMSO. Subsequently, the body weights and the numbers of peripheral white blood cells (WBCs) were measured. Histological analysis of femur bone marrow was conducted to determine the proportion of adipose area as well. Finally, the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) in bone marrow was detected by immunohistochemistry. After irradiation, the percentage of adipose area in the bone marrow was significantly increased, and the WBC number and body weight were markedly reduced. Compared with irradiation alone, the co-administration of 1,25-(OH)2D3 with irradiation markedly attenuated radiation-induced adipogenesis in bone marrow, resulted in fewer bone marrow stromal cells expressing PPARgamma and enhanced the recovery of body weight and WBCs. These results indicate that 1,25-(OH)2D3 could accelerate the recovery of body weight and WBCs in irradiated mice and protect the bone marrow by inhibiting radiation-induced adipogenesis via the down-regulation of PPARgamma expression.
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