Journal of Korean Endocrine Society 1997;12(2):215-221.
Published online January 1, 2001.
Changes of Bone Mineral Density and Levels of Cytokines in the Culture Media of Bone Marrow Monocytes after Ovariectomy in Rats.
Keun Yong Park
Although the mechanism of the increase in bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvironment and influence bone remodeling. Among them, IL-1 and TNF-a promote bone resorption by stimulating the activity of mature osteoclasts and the differentiation of osteoclast precursors and the production of these cytokines are mediated by estrogen. We performed this study to evaluate the effect of ovariectomy on bone mineral density and levels of cytokines in the culture media of bone marrow monocytes. METHODS: The experimental animals were 23 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 176.8 gm at the beginning of the study. Bilateral ovariectomy (n=13) and sham-operation (n=10) were performed in all rats from a ventral approach. Bone mineral density (BMD) of the total body and levels of IL-1 and TNF-a of culture media of bone marrow monocytes were measured before and 8 weeks after operation with using DPX-L and ELISA assay, respectively. Serum levels of LH, FSH, E2 were measured by RIA assay. RESULTS: BMD of total body was lower after ovriectomy (0.24+-0.04g/cm) than before ovariectomy (0.27+-0.03g/cm), but there was no statistically significant difference in sham-operation group. Serum levels of LH, FSH were higher after ovariectorny (0.87+-0.36 mIU/mL, 9.47+-1.26 mIU/mL) than before ovariectomy (0.10+-0.06mIU/mL, 2.09+-0.41mIU/mL) (p<0.01) and serum level of E was lower after ovariectomy (10.98+-8.71pg/mL) than before ovariectomy (7350.77+-417.29 pg/mL) (p<0.01), respectively. Levels of IL-1 and TNF-a in culture media of bone marrow monocytes were higher after ovariectomy (23.48+-3.98pg/mL, 52.64+-5.31 pg/mL) than before ovariectomy (9.72+0.94pg/mL, 24.37+-3.39pg/mL) (p<0.01), but there were no statistically significant differences in the sharn-operation group. CONCLUSION: It is possible that increased production of IL-1 and TNF-a in estrogen deficiency induced by ovariectomy occures in the bone microenvironment and these cytokines may play a critical causal role in inducing bone loss.
Key Words: Ovariectomy, IL-1, TNF-a
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