Effect of genistein on the expression of bone metabolism genes in ovariectomized mice using a cDNA microarray.
Osteoporosis associated with estrogen deficiency is defined as an abnormal decrease in bone mass leading to an increased fracture risk. Genistein (GEN), as a phytoestrogen, is a type of soybean-derived isoflavone that possesses structural similarity to estrogen. In this study, we assessed the effect of GEN in ovariectomized (OVX) mice. To determine the effect of GEN on bone metabolism, we investigated gene expression profiles using a radioactive cDNA microarray. Eight-week-old female mice were either sham operated (SHAM) or OVX. From 1 week after the operation, OVX mice were injected daily with intraperitoneal GEN (0.1, 0.5, 1.5 and 3.0 mg/day) or 17beta-estradiol (E2, 0.03 microg/day) for 4 weeks. A cDNA microarray was used to evaluate changes in the expression of 1,152 genes. OVX mice showed bone mineral density (BMD) loss versus SHAM mice (5.8+/-0.4 vs. 6.9+/-0.6 mg/cm2). However, femur BMDs were completely restored by GEN and by E2 administration in OVX mice. Serum osteocalcin in OVX mice treated with 0.5 mg/day of GEN was 1.6-fold (44.30+/-5.73 ng/ml) higher than that in untreated mice. GEN treatment up-regulated 38 genes (e.g., mitogen-activated protein kinase 10) and down-regulated 18 (e.g., matrix metalloproteinase 13). Moreover, GEN was found to have a protective effect on bone loss caused by estrogen deficiency in OVX mice. The present study suggests that GEN modulates bone metabolism-related gene expression, including calciotropic receptor, cytokines, growth factors and bone matrix proteins.
Pie
Jae-Eun
JE
Department of Food and Nutrition, College of Science and Engineering, Anyang University, Anyang 430-714, Korea.
Park
Jin-Hee
JH
Park
Yoon-Hee
YH
Ryu
Yeon-Mi
YM
Kim
Ki-Nam
KN
Suh
Seung-Woo
SW
Becker
Kevin G
KG
Cho-Chung
Yoon S
YS
Kim
Meyoung-Kon
MK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D005269:Femur; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D053509:Matrix Metalloproteinase 13; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010052:Ovariectomy; D014599:Uterus / Q000033:anatomy & histology
D016207:Cytokines; D018076:DNA, Complementary; D006133:Growth Substances; D015675:Osteocalcin; D004958:Estradiol; D019833:Genistein; D020928:Mitogen-Activated Protein Kinases; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse