Expression of Estrogen Receptors α and β in Human Osteoblasts: Identification of Exon-2 Deletion Variant of Estrogen Receptor β in Postmenopausal Women

Background: Postmenopausal osteoporosis is associated with estrogen deficiency. Estrogens have effects on bone metabolism, which are mediated by estrogen receptors (ERs). If estrogen responsiveness is related to the ER expression level, ER expression in postmenopausal women should be different from previous studies using osteoblast lineage. We investigated the expression of variant isoforms of ER messenger ribonucleic acid (mRNA) in osteoblasts (OB) from postmenopausal women and a human osteosarcoma cell line, MG 63. Methods: Osteoblast cultures were prepared from the upper femur of postmenopausal patients or MG 63. For OB cultures at 5, 10, 15, 20, and 25 days, the expressions of ERα and β mRNA were examined using reverse transcriptase-polymerase chain reaction. Results: In MG 63, ERβ mRNA was constantly and highly expressed during the 25-day culture, whereas ERα mRNA was barely detected. In the primary OB cells, both ERα and β mRNA were transcribed during the 25-day culture, but expression of ERα mRNA was much stronger than that of ERβ mRNA. A splice variant form of ERβ mRNA that was missing the entire exon 2 (ERβ Δ2) was detected and heterogeneously expressed in OB cultures from 16 postmenopausal women. Conclusion: Differential expressions of these ER isoforms suggest that they may have different functions or that they interact with each other during bone metabolism. The different ratio of ERβ to ERβ Δ 2 mRNA or ERα to ERβ mRNA expressions in osteoblast cultures may be related to different bone conditions. Whether the presence of ERβ Δ 2 in postmenopausal women influences the biological properties of bone needs to be determined.