自噬在骨保护素对破骨细胞及其前体凋亡过程的调控机制

doi:10.11843/j.issn.0366-6964.2018.08.022

Abstract

Abstract:

In order to investigate the effects of osteoprotegerin (OPG) on autophagy and apoptosis in osteoclasts (OCs) and osteoclast precursors (OCPs), RAW264.7 cells were pretreated with autophagy promoter rapamycin (RAP) for 1 h or autophagy inhibitor chloroquine (CQ) for 30 min, followed by treatment with 80 ng·mL^-1 OPG for another 6 h, and cells were divided into the Control group (Con), the OPG group, the CQ group, the CQ +OPG group, the RAP group and the RAP+OPG group, Western blot was applied to detect the proteins related to autophagy; Flow cytometry was used to observe the apoptosis rate. The results of Western blot showed that in OCPs treated with OPG the expression of Atg5 was increased significantly (P<0.01) and Beclin-1 was increased (P<0.05), while the expression of LC3-Ⅱ showed no significant difference (P>0.05) compared with Con group; Compared with OPG treatment group, the expression of LC3-Ⅱ was significantly increased in the RAP+OPG group. In OCs, compared with Con group, OPG treatment markedly reduced (P<0.01) the expression of LC3-Ⅱ, Atg5 and Beclin-1; Compared with the OPG group, the expression of Atg5 and Beclin-1 were significantly reduced by the combination use of RAP+OPG. The results of flow cytometry showed that in OCPs, OPG and RAP, alone or in combination, markedly increased the apoptosis rate (P<0.01),while there was no difference (P>0.05) in the CQ+OPG group; The effect of RAP+OPG was stronger compared to the OPG treatment group (P<0.01). While in OCs, the apoptosis level was greatly reduced by OPG (P<0.01), both CQ+OPG and RAP+OPG presented significantly decreased apoptosis level (P<0.01). The results of our study demonstrate that OPG induces apoptosis of OCPs by activating autophagy. Nevertheless OPG reduces apoptosis of OCs through restraining the autophagy in OCs. Interestingly, either the inhibition or promotion of autophagy results in the apoptosis of OCs.

CLC Number:

S813.1

LIU Qing-yang, SUN Zi-qiang, ZHAO Hong-yan, SONG Rui-long, GU Jian-hong, LIU Zong-ping. Effects of Autophagy on the Apoptosis of Osteoclasts and Osteoclast Precursors Mediated by Osteoprotegerin[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(8): 1761-1769.

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Effects of Autophagy on the Apoptosis of Osteoclasts and Osteoclast Precursors Mediated by Osteoprotegerin

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