All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Abstract

Mechanism of Activation of AMPK/P53-CyPD Signaling Pathway in Inhibiting Osteoblast Apoptosis Induced by Dexamethasone

Author(s): Z. Guo, L. Zhu, C. Yin, Y. Liu, J. Fang and Y. Zhen*
Department of Orthopaedics, Children’s Hospital of Soochow University, Suzhou Industrial Park, No.92 Zhongnan Street, Suzhou, Jiangsu Province, China

Correspondence Address:
Department of Orthopaedics, Children’s Hospital of Soochow University, Suzhou Industrial Park, No.92 Zhongnan Street, Suzhou, Jiangsu Province, China, E-mail: [email protected]

The objective of this study was to investigate the role of AMPK/P53-CyPD signaling pathway in osteoblast apoptosis induced by dexamethasone and to confirm that the activation of adenosine monophosphate-activated protein kinase signaling pathway can delay the progression of osteonecrosis of the femoral head and promote the regeneration of osteoblasts. In this study, 24 C57BL/6J 8-week old mice were selected as research subjects, which were randomly divided into the model group, the blank group and the intervention group, with 8 mice in each group. The model group was given subcutaneous injection of dexamethasone, the blank group was given subcutaneous injection of the same dose of normal saline, and the intervention group was given intraperitoneal injection of cyclophilin D (CyPD) inhibitor and P53 inhibitor on the basis of the model group. Eight weeks after the experiment, all mice were sacrificed, femoral head samples were taken for nuclear magnetic resonance and micro CT scanning, and the femoral head tissue samples were made for H and E staining to analyze the effect of inhibiting the AMPK/P53-CyPD signaling pathway on the femoral head structure in mice. Then, the AMPK α-expressing osteoblast cell line was constructed by exogenously adding the AMPK activator acadesine to the femoral head tissue of the model group. The cell survival cycle and apoptosis of osteoblasts were observed. The results showed that firstly, the morphology of the femoral head in the model group changed, the bone trabecula became thinner, the continuity was destroyed and the subchondral bone was partially necrotic. The morphology of the femoral head in the intervention group was significantly changed, the bone density decreased and the bone marrow cavity increased significantly and the structure of the normal femoral head was lost. The number of bone cells in the lacuna was significantly decreased. Secondly, after the exogenous addition of acadesine, the AMPK signaling pathway was activated, the apoptosis was gradually improved and the formation of osteoblasts was significantly increased. It could be concluded that the AMPK/P53-CyPD signaling pathway plays an important role in osteoblast apoptosis induced by dexamethasone, which can inhibit osteoblast apoptosis, delay the process of femoral head osteonecrosis, and promote the recovery of femoral head osteonecrosis.

Full-Text | PDF