Open AccessA quinoxaline-based compound ameliorates bone loss in ovariectomized mice
Author(s) -
Ying Zhou,
Xiaoyan Xue,
Yanyan Guo,
Huan Liu,
Hui Zheng,
Chen Zhou,
Ning Wang,
Fen Li,
Yang Wang
Publication year - 2021
Publication title -
experimental biology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 146
eISSN - 1535-3702
pISSN - 1535-3699
DOI - 10.1177/15353702211032133
Subject(s) - ovariectomized rat , quinoxaline , chemistry , endocrinology , medicine , pharmacology , estrogen , organic chemistry
DMB (6,7-dichloro-2-methylsulfonyl-3-Ntert-butylaminoquinoxaline) is a quinoxaline-based compound that has been investigated as a glucagon-like peptide-1 receptor (GLP-1R) agonist. To clarify anti-osteoporosis effect of DMB, an osteoporotic mice model was established by ovariectomy (OVX) operation. The OVX mice were given intraperitoneally DMB, exendin-4 (EX-4), or 17β-estradiol (E 2 ) for two months. Then bone mass and structure, and bone morphometric parameters were examined by micro-CT. Weight gain and food consumption, bone turnover markers, and biomechanical strength of the femur were tested, and bone histomorphometry was analyzed. The food intake and weight gain was obviously reduced by E 2 or EX-4, but not DMB. However, DMB or EX-4 treatment obviously inhibited skeletal deterioration and enhanced bone strength. The improvement involved in the increased osteoblast number and level of bone formation markers, and reduced osteoclasts number and level of bone resorption markers. In addition, DMB was found to stimulate osteoblastogenesis-related marker gene expression. These results demonstrated that DMB ameliorated bone loss mainly via induction of bone formation, which suggests that the small molecule compound might be applied to the management of postmenopausal osteoporosis.