INDUCTION OF OSTEOCLAST FORMATION BY PARATHYROID-HORMONE DEPENDS ON AN ACTION ON STROMAL CELLS

It is believed that parathyroid hormone (PTH) increases the resorptive activity of pre-existing osteoclasts through a primary interaction wi th cells of the osteoblastic lineage. Much less is known, however, of the mechanisms by which PTH induces osteoclast formation. It is known that osteoclast formation occurs through a contact-dependent interacti on between stromal cells and haemopoietic precursors, but it is not kn own whether PTH acts on stromal cells or precursors to induce osteocla st formation. To address this issue, we compared the ability of haemop oietic cultures to generate osteoclasts, identified as calcitonin rece ptor positive (CTRP) cells, and to resorb bone in response to PTH and 1,25(OH)(2) vitamin D-3 (1,25(OH)(2)D-3). We found that when murine ha emopoietic tissues were incubated at densities sufficiently high to su pport haemopoiesis, both PTH and 1,25(OH)(2)D-3 induced bone resorptio n in bone marrow cells, but in cultures of haemopoietic spleen only 1, 25(OH)(2)D-3 induced CTRP cells, and neither hormone induced bone reso rption. To determine whether these differences were attributable to di fferences in stromal cells or haemopoietic precursors, lower densities of haemopoietic spleen cells were incubated on osteoblastic (UMR 106) , splenic or bone marrow stromal cells. We found that the behaviour of the cocultures reflected the characteristics and origin of the stroma l cells. Thus, the ability of both osteoblastic and splenic stromal ce lls to induce CTRP cells with 1,25(OH)(2)D-3, while only osteoblastic cells induced osteoclasts with PTH, from the same precursors, suggests that the ability of PTH to induce osteoclastic differentiation cannot be attributed to a hormonal action on osteoclast precursors, but depe nds on a response in stromal cells.