Abstract: FR-PO600

FK506 Attenuates Bone Loss by Inhibiting Endothelial-to-Adipocyte Transition in Diabetic Rats

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental


  • Ni, Li-Hua, Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China, Nanjing, Jiangsu, China
  • tang, rining, Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
  • Song, Kaiyun, Southeast University School of Medicine, Nanjing, Jiangsu, China
  • Liu, Bi-Cheng, Zhong Da Hospital, Southeast University Medical School, Nanjing, JIANGSU , China

FK506, a well known immunosuppressant drugs, was found to be beneficial for bone health recently. However, the underlying mechanism is still under study. Our previous research has shown that high glucose induced phenotypic changes of endothelial cells (EndMT) in vivo and in vitro. Therefore, we asked the question of whether high glucose induced EndMT could be transformed to MSCs and differentiated into adipocytes (endothelial-to-adipocyte transition), and subsequently be involved in the bone loss in diabetes.


Diabetic rats were divided into two groups: the diabetic group (DM) and the FK506-treated group (DM+FK506). Diabetic models were established by intraperitoneal injection with streptozocin. Healthy rats served as control (CTL). Skeletal changes were determined by dual energy x-ray absorption (DEXA), micro-computed tomography (micro-CT), and bone mechanics tests. Immunofluorescence staining was performed to detect the co-expression of endothelial marker (CD31) and fibroblast marker (FSP1), CD31 and adipocyte marker (LPL). The expression of CD31, FSP1, mesenchymal stem cell markers (CD10, CD44, STRO-1), and LPL were detected by immunohistochemistry, real time-PCR and western blots. Adipocytes were detected by oil red O staining.


Increased bone loss was detected in the DM group, which could be attenuated by FK506 treatment: the bone mineral density (BMD) of femur and lumbar assessed by DEXA were decreased in the DM group, which attenuated by FK506 treatment (P<0.05); the trabecular BV/TV, trabecular number, cortical area, cortical thickness measured by micro-CT were decreased in the DM group, which were alleviated in the DM+FK506 group (P<0.05). The adipocytes infiltration in the DM group detected by oil red O staining was significantly increased compared with the CTL group, which was improved by FK506 treatment (P<0.05). The expression of CD31 was notable down-regulated in DM group, whereas the expressions of FSP1, CD10, CD44, STRO-1, LPL were markedly up-regulated. These changes were inhibited by FK506 treatment (P<0.05).


This study provides a novel insight that bone marrow endothelial-to-adipocyte transition might contribute to the bone loss in diabetes, and FK506 treatment could attenuate the skeletal changes by inhibiting this phenotypic transition.


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