Open AccessHarmine targets inhibitor of DNA binding‐2 and activator protein‐1 to promote preosteoclast PDGF‐BB production
Author(s) -
Huang Jie,
Li YouYou,
Xia Kun,
Wang YiYi,
Chen ChunYuan,
Chen MengLu,
Cao Jia,
Liu ZhengZhao,
Wang ZhenXing,
Yin Hao,
Hu XiongKe,
Wang ZhengGuang,
Zhou Yong,
Xie Hui
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16562
Subject(s) - harmine , activator (genetics) , osteoclast , platelet derived growth factor receptor , rankl , chemistry , gene knockdown , microbiology and biotechnology , growth factor , cancer research , biology , biochemistry , pharmacology , in vitro , gene , receptor
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.