the Effect of Genistein on Alveolar Bone Resorption in Vitro and in Vivo

Objective: To investigate the effect of genistein, a soybean-derived isoflavone, on the osteoclastic bone resorption in vitro and in vivo. Methods: Primary osteoclast-like cells (OLCs) were exposed to genistein at various concentration.The number of TRAP+ cells was counted as well as the surface area of bone resorption on bone slice. The mRNA level of RANKL and OPG were tested by RT-PCR. Additionally, forty 12 wk-old female SD rats were randomly assigned to four groups: ¢Ùsham operated (Sham group); ¢Úovariectomized (OVX group); ¢Ûovariectomized and treated with estradiol (E group); ¢Üovariectomized and received genistein (G group). After 12 weeks, alveolar bone, mandible,tibia and uteri were fetched and sectioned. The indexes of distance of double label(DDL) and mineral appositional rate (MiAR) were calculated under the fluorescent microscope. The serum estradiol were also examined by immunoradiometric assay. Results: In vitro, the number of TRAP+ cells decreased depending on the concentration of genistein as well as the area of bone resorption. Genistein could enlarge the ratio between the mRNA level of OPG and RANKL in the pattern of dosage-depended and time-depended. Histologically, there were more osteoblasts attached in the alveolar and mandible in G group and no osteoclastic bone resorption were observed after treated with genistein. The indexes of DDL and MiAR were also decreased after treated with genistein. The uterus weight index and the serum estradiol in G group rats were lower than those of E group. The epithelia of uteri gland in G group appeared cubic while those of E group became squamous. Conclusion: Genistein inhibited OLCs' bone resorption through suppression the differentiation of pre-osteoclasts, and the ratio between OPG and RANKL may be the key factor. Histologically genistein can prevent osteoclastic bone resorption and stimulate bone formation in vivo with slight side effect on the uteri.