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8‐Prenylgenistein, a prenylated genistein derivative, exerted tissue selective osteoprotective effects in ovariectomized mice
Author(s) -
Zhang Yan,
Li Xiaoli,
Wang Yongjun,
Wong ManSau
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.967.10
Subject(s) - ovariectomized rat , genistein , endocrinology , medicine , chemistry , estrogen , phytoestrogens , osteocalcin , uterus , biochemistry , alkaline phosphatase , enzyme
Our previous studies reported that the in vitro osteogenic effects of 8‐prenylgenistein (8PG) were more potent than its parent compound genistein in osteoblastic UMR 106 cell. This study aimed to study the in vivo osteoprotective effects of 8PG in ovariectomized (OVX) mice as well as to characterize its estrogenic effects in uterus. Mature OVX C57BL/6J mice were treated with phytoestrogen‐free AIN‐93M diet containing 8PG (300 & 600 ppm) or genistein (300 ppm) for 7 weeks. Trabecular bone properties, mRNA and protein expression in bone and uterus were determined. The potential estrogenic effects in uterus and endometrial Ishikawa cells were evaluated. Trabecular bone mass and most of the micro‐structural parameters were significantly ameliorated at the distal metaphysis of femur in OVX mice upon treatment with genistein and both doses of 8PG. The beneficial effects of 8PG on trabecular bone and articular chondrocytes in OVX mice were confirmed by safranin O and ABHO staining and the 3D micro‐CT image. 8PG markedly inhibited the OVX‐induced mRNA expressions of RANKL/OPG, ALP, type 1 collagen, osteocalcin, cathepsin K and estrogen receptor alpha (ER‐α) in bone. In contrast, genistein further increased the OVX‐induced ER‐α expression in bone. The uterus index was increased in genistein‐treated group, but not in 8PG‐treated groups. Genistein up‐regulated the expression of ER‐α and PR, while 8PG significantly down‐regulated the ER‐α and C3 expression in the uterus of OVX mice. Moreover, genistein, but not 8PG, increased expressions of ER‐α and PCNA in Ishikawa cell. Competitive binding assay showed that the ability of genistein and 8PG to bind ER‐α were comparable, while the binding affinity of 8PG to ER‐β was higher than that of genistein. 8PG improved trabecular bone properties in OVX mice without exerting uterotrophic effects and its estrogenic actions were distinct from those of genistein. Support or Funding Information This work was supported by the Project of National Basic Research Program in China (973 Plan, 2010CB530400), Shenzhen Basic Research Program [JCYJ20140819153305696, JCYJ20140819153305697], Innovative Research Team in University (PCSIRT, IRT1270), the National Natural Science foundation of major international cooperation projects (81220108027 & 81220108028), Longyi Innovation Team Program (LYCX‐01) as well as research support of the Hong Kong Polytechnic University (IBBAB).