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 17β-estradiol (E2, 0.03 μg/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.
Bibliographical noteFunding Information:
The authors thank Dr. Yoon S. Cho-Chung (Cellular Biochemistry Section, Basic Research Laboratory, CCR, NCI, NIH, Bethesda, MD) and Dr. Kevin G. Becker (DNA Array Unit, NIA, NIH, Baltimore, MD) for valuable advices on cDNA microarray. Also, we thank Yeon mi Ryu and Hye won Kim (Department of Biochemistry & Molecular Biology, Korea University Medical School, Seoul, Korea) for valuable advice on this paper. This study was supported by a grant from the Medical Research Center for Environmental Toxicogenomic and Proteomics, funded by the Korea Science and Engineering Foundations and Ministry of Science & Technology, a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (Hmp-00-GN-01-0002 and KPGRN-R-04), a Korea Institute of Science & Technology Evaluation and Planning (KISTEP) and Ministry of Science & Technology (MOST), the Korean government, through its National Nuclear Technology Program, and grant no. R01-2001-000-00212-0 from the Basic Research Program of the Korea Science & Engineering Foundation.
- Bone metabolism
- Gene profiling
- cDNA microarray
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Nutrition and Dietetics
- Clinical Biochemistry