Mechanism of bone resorption induced by estrogen deficiency
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Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. Recent studies on the role of estrogen in bone resorption have focused on the involvement of at least two cytokines, IL-1 and IL-6. It is well known that IL-1 stimulates osteoclastic bone resorptionin vitro andin vivo by inducing the differentiation of osteoclast precursors into mature osteoclasts and by stimulating their activity. On the other hand, we reported that IL-6 greatly stimulated the differentiation of osteoclast precursors into mature osteoclast in the presence of soluble IL-6 receptors in co-cultures of mouse bone marrow and primary osteoblastic cells. Using the systems of ovariectomized (OVX) animals, recent studies have indicated that IL-1 and/or IL-6 are over-produced by bone marrow cells in estrogen deficiency. We examined endogenous bone-resorbing factors present in the supernatants fraction of mouse bone marrows in OVX mice. The endogenous bone-resorbing activity in bone marrow was much greater in OVX mice than in sham mice. The bone-resorbing activity of bone marrow supernatants was significantly decreased by adding indomethacin or neutralizing antibodies against bone-resorbing cytokines such as IL-1α and IL-6. These results suggest that the enhanced bone-resorption that occurs during estrogen deficiency is due to several cytokines including IL-1, IL-6 and prostaglandins rather than to a single factor. Estrogen deficiency induced by OVX stimulated hemopoiesis and caused a marked increase in bone marrow cells. OVX selectively stimulated accumulation of B lymphocyte precursors. This suggests that estrogen modulates the microenvironment for hemopoiesis and bone metabolism in bone marrow.
Key wordsestrogen ovariectomy bone resorption IL-1 IL-6 prostaglandin E
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