Direct and indirect estrogen actions on osteoblasts and osteoclasts.
Cells of osteoblast and osteoclast lineage are provided with the receptor for sex steroids, but discrepancies concerning mechanism of action still exist. Skeletal estrogen (ER) agonists induce osteoblastic osteoprotegerin (OPG) production through ER receptor-alpha activation in vitro, while immune cells appear to overexpress RANKL in ER deficiency in vivo, not reproduced in in vitro study. It has also been evident that the effects of ER on bone to a large extent are mediated via its action on immune cells. We know now that ER regulates the expression of cytokines that target cell types involved in modulating bone turnover, as IL-1 and IL-6, and the latest findings confirm and expand the concept that T cells are key mediators of bone loss following gonadal failure. Although early work demonstrated that tumor necrosis factor-alpha plays an important role in regulating bone mass, recent studies also implicate the lymphopoietic molecule IL-7: it suppresses the bone-forming osteoblasts, while stimulating formation and function of osteoclasts. More recent in vitro studies, however, indicate a stimulating effect of ER on osteoclastogenesis, which could have a positive effect on maintaining a high level of bone cell activity.
Zallone
Alberta
A
Department of Human Anatomy and Histology, University of Bari, Bari, Italy. a.zallone@anatomia.uniba.it
D000818:Animals; D004967:Estrogens / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology
D004967:Estrogens; D006023:Glycoproteins; D012739:Gonadal Steroid Hormones; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human