Prostaglandin E2 promotes osteoclast formation in murine hematopoietic cultures through an action on hematopoietic cells.
Osteoclastic differentiation is induced from hematopoietic cells in the presence of 1,25-(OH)2D3 by stromal cells that are present in bone but not in hematopoietic spleen. Recent evidence suggests that prostaglandins (PGs) are essential for this process. In this communication we describe experiments in which we have examined further the role of PGE2 in osteoclast formation. We found a marked reduction in basal, 1,25-(OH)2D3, and IL-3-induced production of calcitonin receptor (CTR)-positive cells and bone resorption by cyclooxygenase inhibitors, which was restored by PGE2 addition. Although some stromal cell types (ST2 cells) that support osteoclast formation from spleen cells produced PGs in response to 1,25-(OH)2D3, others (ts8 and calvarial cells) did not, either alone or in combination with spleen cells. On the other hand, both bone marrow and spleen cells produced amounts of PGE2 in response to 1,25-(OH)2D3 that were sufficient to account for osteoclast formation. Osteoclast-inductive ts8 cells were able to support osteoclast formation from spleen cells in the presence of 1,25-(OH)2D3 or PGE2 even if devitalized. Incubation of ts8 cells in these agents before devitalization did not avoid the requirement for the presence of PGE2 or 1,25-(OH)2D3 during subsequent incubation with spleen cells. Thus, hematopoietic cells produce sufficient PGE2 for osteoclast formation, and the PGE2 thus produced acts on hematopoietic precursors, which can be induced in the presence of PGE2 to express CTR and resorb bone on contact with osteoclast-inductive stromal cells. The ability of osteoclast-inductive cells to support osteoclast formation appears not to rest on their ability to produce, induce, or respond to PGE2.
Collins
D A
DA
Department of Histopathology, St. George's Hospital Medical School, London, England.
Chambers
T J
TJ
D000818:Animals; D001345:Autoradiography; D001846:Bone Development / Q000187:drug effects*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D015232:Dinoprostone / Q000032:analysis / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007457:Iodine Radioisotopes; D051379:Mice; D008808:Mice, Inbred CBA; D010010:Osteoclasts / Q000187:drug effects*; D012886:Skull / Q000166:cytology
D007457:Iodine Radioisotopes; D015232:Dinoprostone