Figure 5.

Schematic illustrating the roles of estrogen receptor α (ERα) and ERβ at different stages of the osteoblastic lineage. Early osteoblasts can proliferate or differentiate. ERα promotes their proliferation28,39 and either promotes31 or suppresses differentiation.50 There is evidence that ERβ promotes differentiation while inhibiting proliferation. ERβ and ERα both contribute to matrix production, and ERβ also selectively regulates genes associated with cell migration. In osteoblastic cells exposed to mechanical strain, ERα facilitates other osteogenic signaling pathways, specifically insulin-like growth factor (IGF), ERK and Wnt/β-catenin signaling. ERα and ERβ also contribute to anti-apoptotic signaling. Both ERs may also influence osteoclastogenic cytokine expression by osteoblastic cells. This diagram is based on our previous report.34 β-cat, beta-catenin; LRP, low-density lipoprotein receptor related protein.