Rolo of Osteoblastic Cells in Osteoclast Development.

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(1) Studies on stromal cell lines which support osteoclast formation in vitroWe previously reported that osteoclast-like multinucleated cells (MNCs) were formed in response to 1alpha, 25 (OH) _2D_3 in co-cultures of mouse spleen cells and osteoblastic cells freshly isolated from mouse calvariae (Endocrinology, 123 : 2600, 1988). In this study, we examined whether such primary osteoblastic cells can be replaced by established cell lines in inducing osteoclast-like MNC formation. Two bone marrow-derived stromal cell line, MC3T3-G2/PA6 and ST2, were found to suppoort osteoclast-like MNC formation in the co-culture with spleen cells. In addition, a new stromal cell line (KS4), which supports osteoclast-like MNC formation in the co-cultures, was established from mouse calvariae. KS4 cells exhibited typical phenotypes of osteoblasts such as intense alkaline phophatase activity, PTH-dependent cAMP production, and nodule formation in a long-term culture.(2) Origin of osteoclastsWe examined the … More origin of osteoclasts using the co-culture system with ST2 cells. Not only immature hematopoietic cells in bone marrow but also monocytoes in peripheral blood and macrophages in alveolar tissues differentiated into osteoclast-like MNCs in the presence of ST2 cells. This indicates that osteoclasts are the cells of the monocyte-macrophage family.(3) Effects of colony stimulating factors (CSFs) on osteoclast developmentWe examined the effects of CSFs (IL-3, GM-CSF, M-CSF, G-CSF) on the proliferation and the differentiation of osteoclast progenitors. None of the CSFs stimulated differentiation of the progenitors into osteoclast-like MNCs. However, the CSFs, especially M-CSF, markedly stimulated proliferation of the progenitors.The mutation of osteopetrotic (op/op) mice was recently found in the coding region of the M-CSF gene. This indicates that osteoclast deficiency in op/op mice is due to failure of the production of functional M-CSF. We examined osteoclast formation in op/op mice using the co-colture system. We found that osteoblastic cells from op/op mice did not support osteoclast formation in the co-cultures with normal spleen cells. Adding M-CSF to the co-cultures induced the appearance of osteoclast-like cells. These results indicate that M-CSF produced by osteoblastic cells is essential for osteoclast development. Less