Expression data from Dmp1-GFP sorted osteocytes

Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER deletion mice (EROcy/Ocy) were generated by mating ER floxed mice with Dmp1-Cre mice to determine functions of ER in osteocytes. Trabecular bone mineral density of female, but not male EROcy/Ocy mice was significantly decreased. Bone formation parameters in EROcy/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 FACS sorted from EROcy/Ocy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or -catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ER in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.

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Kondoh S, Inoue K, Igarashi K, Sugizaki H, Shirode-Fukuda Y, Inoue E, Yu T, Takeuchi JK, Kanno J, Bonewald LF, Imai Y