Estrogen regulation of gene expression in osteoblasts and osteoclasts

Estrogen has beneficial effects on the maintenance of bone mass and cardiovascular health; however, these are counterbalanced by the potential detrimental effects in reproductive tissues. The paradox of estrogen and bone metabolism is highlighted by the observation that estrogen analogs can act as estrogen antagonists in reproductive tissue while acting as agonists in bone. Estrogen effects on osteoblast and osteoclast gene expression are of critical importance in seeking to understand these contradictory influences. In this review, the in vivo evidence that drives the need for discovery of estrogen effects on bone cells is briefly discussed. In order to better fit this discussion of estrogen actions into a broader context of steroid action, there is a brief review of the cascade model for steroid hormone action and the growing area of nongenomic actions of steroids. This is followed by a more detailed examination of our present knowledge of estrogen effects on osteoblasts and the differentiation and activity of osteoclasts. Direct effects of estrogen on osteoblast-like cell proliferation, cytokine expression, and responses to other stimuli are addressed. The effects of estrogen on cytokine modulation of osteoclastogenesis is examined as well as direct actions of estrogen on osteoclast activity and programmed cell death.