Estrogen Blocks Parathyroid Hormone, Stimulated Osteoclast-Like Cell Formation in Modulating Differentiation of Mouse Marrow Stromal Cells in Vitro

Background and Purpose: During skeletal development and bone remodeling, bone marrow stromal cells give rise osteoblasts and provide a critical microenvironment to support osteoclast formation. Estrogen is important for the maintenance of bone balance in adult animals by either increasing bone mass or, inhibiting osteoclastic bone resorption. This study sought to determine the role that estrogen plays in coordinating osteogenic differentiation of bone marrows stromal cells and the ability of these cells to support osteoclast formation.Methods:A conditionally immortalized mouse bone marrow stromal cell line, MSI. as used to examine the effects of estrogen on stromal cell differentiation and on stromal cell-supported osteoclast formation.Results: On treatment of MSI cells with 17beta- estradiol (E-2) (10(-12)-10(-8) M), alkaline phosphatase activity and bone nodule formation were increased in a dose- dependent manner. while the proliferation of MSI cells was dose-dependently inhibited. 17beta-E-2 (10( -12)-10(-8) M) also caused a concentration-dependent inhibition of tartrate -resistant acid phosphatase (TRAP)-positive multinucleated cell ( MNC) formation in parathyroid hormone (PTH)-stimulated MS1 and spleen Cell cocultures. Furthermore. estrogen pretreatment of NISI cells also decreased the number of TRAP -positive MNCs in cocultures. Culturing in PTH-treated conditioned media did not rescue the loss of activity supporting osteoclast-like cell formation in MS1 cells. Conclusion: These results indicate that 17beta-E-2- stimulated osteoblastic differentiation of mouse marrow stromal cells results in bone matrix mineralization and a decrease in activity of supporting PTH-induced osteoclast- like cell formation