It has been shown that 17β-estradiol (E2) helps to prevent bone loss. This study was undertaken to verify whether E2 action in human osteoblasts involves changes in the transcriptional profile of the TNF-α, IFN-γ, NF-κB, TRAIL, TGF-β, MMP2, MMP9, RECK, TIMP1, TIMP2, CDK2, CDK4, SRC, RUNX2, and SHH genes. Infraphysiological doses of E2 elevated mRNAs in all genes except for INF-γ, TRAIL, and TGF-β. Importantly, a significant increase in the CDKs −2 and −4 genes was found, which strongly suggests cell cycle progression, with a potential dependency of Src involvement, as well as a suppression of the osteoblast differentiation machinery, with ECM remodeling being involved. These data suggest that E2 plays an important role in bone formation and remodeling, and Src seems to play a pivotal role in driving cell proliferation and ECM remodeling. Taken together, these findings contribute to an understanding of the effects of infraphysiological E2 on modulating bone homeostasis, favoring bone resorption, and leading to osteoporosis.

已经显示17β-雌二醇（E2）有助于防止骨质流失。进行这项研究是为了验证人类成骨细胞中E2的作用是否涉及TNF-α，IFN-γ，NF-κB，TRAIL，TGF-β，MMP2，MMP9，RECK，TIMP1，TIMP2，CDK2， CDK4，SRC，RUNX2和SHH基因。在INF-γ，TRAIL和TGF-β以外的所有基因中，E2的基础生理剂量均升高了mRNA的表达。重要的是，发现CDKs -2和-4基因显着增加，这强烈表明细胞周期进程，可能涉及Src参与，并抑制成骨细胞分化机制，并涉及ECM重塑。这些数据表明，E2在骨形成和重塑中起重要作用，而Src似乎在驱动细胞增殖和ECM重塑中起关键作用。