CA2-ATPASE INHIBITORS AND CA2+-IONOPHORE INDUCE OSTEOCLAST-LIKE CELL-FORMATION IN THE COCULTURES OF MOUSE BONE-MARROW CELLS AND CALVARIAL CELLS()

Osteoclasts which derive from hemopoietic cells are multinucleated cel ls responsible for bone resorption. We found that cyclopiazonic acid ( CPA), thapsigargin (TG), and 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) i nduced osteoclast-like cell (OCL) formation in cocultures of mouse cal varia-derived stromal cells and hemopoietic cells such as bone marrow cells and spleen cells. OCLs induced by these compounds showed typical characteristics of osteoclasts such as tartrate-resistant acid phosph atase activity and pit forming activity. These compounds are known as endoplasmic reticulum (ER)/sarcoplasmic reticulum (SR) Ca2+-ATPase inh ibitors that increase intracellular Ca2+ levels by inhibiting Ca2+-ATP ase activity located in the membrane of ER/SR. Ca2+-ionophores such as ionomycin which increase intracellular Ca2+ levels also stimulated OC L formation in the cocultures. Differentiation of hemopoietic cells in to OCLs induced by these compounds required the presence of calvarial cells. These results indicate that an increase of intracellular Ca2+ l evels may be a part of signaling pathways to induce osteoclast differe ntiation in the presence of calvarial cells. (C) 1997 Academic Press.