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Publication : Estrogen receptor-α signaling in osteoblast progenitors stimulates cortical bone accrual.

First Author  Almeida M Year  2013
Journal  J Clin Invest Volume  123
Issue  1 Pages  394-404
PubMed ID  23221342 Mgi Jnum  J:194156
Mgi Id  MGI:5471147 Doi  10.1172/JCI65910
Citation  Almeida M, et al. (2013) Estrogen receptor-alpha signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Invest 123(1):394-404
abstractText  The detection of estrogen receptor-alpha (ERalpha) in osteoblasts and osteoclasts over 20 years ago suggested that direct effects of estrogens on both of these cell types are responsible for their beneficial effects on the skeleton, but the role of ERalpha in osteoblast lineage cells has remained elusive. In addition, estrogen activation of ERalpha in osteoclasts can only account for the protective effect of estrogens on the cancellous, but not the cortical, bone compartment that represents 80% of the entire skeleton. Here, we deleted ERalpha at different stages of differentiation in murine osteoblast lineage cells. We found that ERalpha in osteoblast progenitors expressing Osterix1 (Osx1) potentiates Wnt/beta-catenin signaling, thereby increasing proliferation and differentiation of periosteal cells. Further, this signaling pathway was required for optimal cortical bone accrual at the periosteum in mice. Notably, this function did not require estrogens. The osteoblast progenitor ERalpha mediated a protective effect of estrogens against endocortical, but not cancellous, bone resorption. ERalpha in mature osteoblasts or osteocytes did not influence cancellous or cortical bone mass. Hence, the ERalpha in both osteoblast progenitors and osteoclasts functions to optimize bone mass but at distinct bone compartments and in response to different cues.
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