Article: Melville, KM; Kelly, NH; Surita, G; Buchalter, DB; Schimenti, JC; Main, RP; Ross, FP; van der Meulen, MCH; (2015) “Effects of Deletion of ER in Osteoblast-Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice”, Journal of Bone and Mineral Research, 30 (8):1468-1480
Abstract: Estrogen receptor alpha (ER) has been implicated in bone’s response to mechanical loading in both males and females. ER in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ER is deleted. We demonstrated previously that when ER is deleted from mature osteoblasts and osteocytes in mixed-background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell-specific ERKO mice. Therefore, we crossed ER floxed (ERfl/fl) and osteocalcin-Cre (OC-Cre) mice to generate animals lacking ER in mature osteoblasts and osteocytes (pOC-ERKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro-CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ER in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC-ERKO mice had decreased cortical and cancellous bone mass, whereas male pOC-ERKO mice had equal or greater bone mass than LC.
Bone mass results correlated with decreased compressive strength in pOC-ERKO female L-5 vertebrae and with increased maximum moment in pOC-ERKO male femora. Female pOC-ERKO mice responded more to mechanical loading, whereas the response of pOC-ERKO male animals was similar to their littermate controls. (c) 2015 American Society for Bone and Mineral Research. (c) 2015 American Society for Bone and Mineral Research.
Funding Acknowledgement: National Institutes of Health [R01-AG028664, P30-AR046121]; NSF GRFP; [F32-AR054676]
Funding Text: Financial support was provided by National Institutes of Health grants R01-AG028664 and P30-AR046121 (MCHM), NSF GRFP (KMM and NHK), and F32-AR054676 (RPM).