Deficiency of osteoclasts in osteopetrotic mice is due to a defect in the local microenvironment provided by osteoblastic cells.
Deficiency of osteoclasts in osteopetrotic mice is due to a defect in the local microenvironment provided by osteoblastic cells.
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DOI：
10.1210/endo-128-4-1792
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发表时间：
1991-04
期刊：
影响因子：
4.8
通讯作者：
N. Takahashi;N. Udagawa;T. Akatsu;Hirofumi Tanaka;Y. Isogai;T. Suda
中科院分区：
文献类型：
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作者：
N. Takahashi;N. Udagawa;T. Akatsu;Hirofumi Tanaka;Y. Isogai;T. Suda
我们曾报道脾组织中的破骨祖细胞分化为多核破骨细胞需要成骨细胞。在本研究中，我们研究了破骨细胞缺乏的发病机制，在骨硬化（OP/OP）小鼠使用的脾细胞和成骨细胞的共培养系统。当从op/op或正常获得脾细胞时（+/？）将op/+亲代小鼠的同窝仔与从正常ddy品系小鼠的颅骨获得的成骨细胞共培养，在1 α，25-二羟基维生素D3 [1 α，25（OH）2D 3]存在下形成许多抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞（MNC）。大多数TRAP阳性MNC结合[125 I]鲑鱼降钙素。这表明op/op小鼠脾组织中存在的破骨细胞祖细胞没有异常。当成骨细胞从+/？将同窝出生的小鼠与来自ddy小鼠的正常脾细胞共培养，TRAP阳性MNC响应于1 α，25（OH）2D 3而类似地形成。相反，在与正常脾细胞共培养的op/op成骨细胞中，即使在1 α，25（OH）2D 3的存在下，也没有TRAP阳性细胞出现。最近报道了巨噬细胞集落刺激因子（M-CSF）基因编码区存在op/op突变。将M-CSF和1 α，25（OH）2D 3加入到与op/op成骨细胞的共培养物中诱导了具有降钙素受体的TRAP阳性MNC的出现。这些结果清楚地表明，OP/OP小鼠中的破骨细胞缺乏是由于骨中局部微环境的缺陷，其中成骨细胞产生的M-CSF在破骨细胞发育中起关键作用。
We have reported that osteoblastic cells are required for differentiation of osteoclast progenitors in splenic tissues into multinucleated osteoclasts. In the present study we examined the pathogenesis of the osteoclast deficiency in osteopetrotic (op/op) mice using a coculture system of spleen cells and osteoblastic cells. When spleen cells obtained from op/op or normal (+/?) littermates of op/+ parent mice were cocultured with osteoblastic cells obtained from calvaria of normal ddy strain mice, numerous tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) were formed in the presence of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. Most of the TRAP-positive MNCs bound [125I]salmon calcitonin. This suggests that there is no abnormality in the osteoclast progenitors present in the splenic tissues of op/op mice. When osteoblastic cells from +/? littermates were cocultured with normal spleen cells from ddy mice, TRAP-positive MNCs were similarly formed in response to 1 alpha,25(OH)2D3. In contrast, in cocultures of op/op osteoblastic cells with normal spleen cells, no TRAP-positive cells appeared, even in the presence of 1 alpha,25(OH)2D3. The op/op mutation was recently reported to exist in the coding region of the macrophage colony-stimulating factor (M-CSF) gene. Adding M-CSF and 1 alpha,25(OH)2D3 to the coculture with op/op osteoblastic cells induced the appearance of TRAP-positive MNCs with calcitonin receptors. These results clearly indicate that osteoclast deficiency in op/op mice is due to a defect in the local microenvironment in bone, in which M-CSF produced by osteoblastic cells plays a critical role in osteoclast development.