Estrogen receptor ? in osteocytes regulates trabecular bone formation in female mice.

ABSTRACT: Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, in which estrogen signaling may intersect with the Wnt/?-catenin pathway, is essential for bone maintenance. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER? deletion mice (ER?(?Ocy/?Ocy)) were generated by mating ER? floxed mice with Dmp1-Cre mice to determine the role of ER? in osteocytes. Trabecular bone mineral density of female, but not male ER?(?Ocy/?Ocy) mice was significantly decreased. Bone formation parameters in ER?(?Ocy/?Ocy) were significantly decreased while osteoclast parameters were unchanged. This suggests that ER? in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ER?, gene array analysis of Dmp1-GFP osteocytes sorted by FACS from ER?(?Ocy/?Ocy) and control mice was performed. Gene expression microarray followed by gene ontology analyses revealed that osteocytes from ER?(?Ocy/?Ocy) highly expressed genes categorized in 'Secreted' when compared to control osteocytes. Among them, expression of Mdk and Sostdc1, both of which are Wnt inhibitors, was significantly increased without alteration of expression of the mature osteocyte markers such as Sost and ?-catenin. Moreover, hindlimb suspension experiments showed that trabecular bone loss due to unloading was greater in ER?(?Ocy/?Ocy) mice without cortical bone loss. These data suggest that ER? in osteocytes has osteoprotective functions in trabecular bone formation through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.

SUBMITTER: Kondoh S 

PROVIDER: S-EPMC3944732 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature