| Co-Investigator(Kenkyū-buntansha) |
SASAKI Takahisa Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (50129839)
TAKITO Jiro Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (00197237)
SUDA Tatsuo Showa Univ., School of Dentistry Professor, 歯学部, 教授 (90014034)
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| Research Abstract |
We have developed a co-culture system of mouse osteoblastic cells and spleen cells to investigate the interaction of osteoclast progenitors with osteoblastic cells in their differentiation into osteoclasts.Using this co-culture system, we examined [1] role of osteoblastic cells in osteoclast development, [2] pathogenesis of osteopetrotic disorders in op/op (osteopetrotic) and oc/oc (osteosclerotic) mutant mice, and [3] expression of p60^<c-src> (a product of c-src proto-oncogenen) in osteoclasts.
[1] Role of Osteoblastic Cells in Osteoclast Development The role of osteoblastic cells in osteoclast development was investigated in a co-culture system of mouse osteoblastic cells and spleen cells. We have shown that osteoblastic cells play an important role in modulating the differentiation of osteoclast progenitors through a mechanism of cell-to-cell interaction (5,6,8). The expression of an osteoclast-inducing factor (s) by osteoblastic cells appeared to be tightly regulated by bone-resorb
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ing factors such as 1alpha,25-dihydroxyvitamin D_3 and parathyroid hormone (1,2,6,11).
[2] Pathogenesis of Osteopetrotic Disorders in Mutant Mice We examined pathogenesis of osteopetrotic disorders in op/op and oc/oc mutant mice using a co-culture system of their osteoblastic cells and spleen cells. It was shown that osteoclast deficiency in op/op mice is due to a defect in osteoblastic cells, and that the M-CSF produced by osteoblastic cells plays a critical role in osteoclast development (3). We also found that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts (4, 10). In experiments using oc/oc mice, we concluded that the lack of bone resorption in oc/oc mice is due to a defect of osteoclast progenitors, which fail to differentiate into functional osteoclasts in the microenvironment provided by osteoblastic cells (7).
[3] Expression of p60^<c-src> in Osteoclasts Recently, it was reported that the targeted disruption of c-src in mice induced osteopetrosis. We, therefore, examined expression of p60^<c-src> in authentic osteoclasts and osteoclast-like cells formed in the co-culture system. The expression of p60^<c-src> strikingly increased parallel with the appearance of osteoclast-like cells in the co-culture (9). The electron microscopic study revealed that p60^<c-src> was primarily localized on ruffled border membranes and vacuoles (9). These results indicate that p60^<c-src> is important in osteoclastic bone resorption. Less
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