Article Publish Status: FREE
Abstract Title:

Harmine targets inhibitor of DNA binding-2 and activator protein-1 to promote preosteoclast PDGF-BB production.

Abstract Source:

J Cell Mol Med. 2021 06 ;25(12):5525-5533. Epub 2021 May 7. PMID: 33960660

Abstract Author(s):

Jie Huang, You-You Li, Kun Xia, Yi-Yi Wang, Chun-Yuan Chen, Meng-Lu Chen, Jia Cao, Zheng-Zhao Liu, Zhen-Xing Wang, Hao Yin, Xiong-Ke Hu, Zheng-Guang Wang, Yong Zhou, Hui Xie

Article Affiliation:

Jie Huang


Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet-derived growth factor-BB (PDGF-BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF-BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding-2 (Id2) and activator protein-1 (AP-1) were important factors implicated in harmine-enhanced preosteoclast PDGF-BB production. Exposure of RANKL-induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP-1. Knockdown of Id2 by Id2-siRNA reduced the number of preosteoclasts as well as secretion of PDGF-BB in RANKL-stimulated BMMs administrated with harmine. Inhibition of c-Fos or c-Jun (components of AP-1) both reversed the stimulatory effect of harmine on preosteoclast PDGF-BB production. Dual-luciferase reporter assay analyses determined that PDGF-BB was the direct target of AP-1 which was up-regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF-BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Osteoprotective : CK(971) : AC(351)

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