STIMULATORY EFFECT OF BONE MORPHOGENETIC PROTEIN-2 ON OSTEOCLAST-LIKE CELL-FORMATION AND BONE-RESORBING ACTIVITY
STIMULATORY EFFECT OF BONE MORPHOGENETIC PROTEIN-2 ON OSTEOCLAST-LIKE CELL-FORMATION AND BONE-RESORBING ACTIVITY
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DOI：
10.1002/jbmr.5650101110
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发表时间：
1995-11-01
影响因子：
6.2
通讯作者：
CHIHARA, K
中科院分区：
文献类型：
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作者：
KANATANI, M;SUGIMOTO, T;CHIHARA, K
骨形态发生蛋白（bone morphogenetic protein， BMP）在成骨细胞分化中的作用已被广泛研究，但其对破骨细胞分化的影响尚不清楚。本研究考察了体外BMP-2对破骨细胞样细胞形成和骨吸收的影响。BMP-2 （1-100 ng/ml）显著刺激含有基质细胞的小鼠骨细胞培养物中先前存在的破骨细胞样细胞的骨吸收，而不影响兔离体破骨细胞样细胞的骨吸收活性。当先前存在的破骨细胞样细胞变性后，将BMP-2添加到未分离的骨细胞中，BMP-2以最小有效浓度10 pg/ml的剂量依赖性刺激破骨细胞样细胞的形成。BMP-2还能促进1,25-二羟基维生素D-3 (1,25（OH)(2)D-3）诱导的破骨细胞样细胞形成。此外，未分离的骨细胞中BMP-2新形成的破骨细胞样细胞具有在牙本质切片上形成凹坑的能力。由于这些结果表明BMP-2直接或间接地刺激破骨细胞的分化和活性，我们接下来使用来自脾细胞的造血母细胞检测BMP-2在缺乏基质细胞的情况下对破骨细胞前体的直接影响。通过RNase保护实验检测了粒细胞-巨噬细胞集落刺激因子（GM-CSF）支持的造血母细胞、成骨细胞MC3T3-E1细胞和MC3T3-G2/PA6基质细胞中BMP-2受体mRNA的表达，发现GM-CSF支持的造血母细胞在最低有效浓度为10 pg/ml时，BMP-2剂量依赖性地刺激了破骨细胞样细胞的形成。BMP-2还能增强造血母细胞中1,25(OH)(2) d -3诱导的破骨细胞样细胞的形成。目前的数据首次表明BMP-2通过直接刺激破骨细胞形成和激活成熟破骨细胞（可能通过基质细胞）来刺激骨吸收。
Although the action of bone morphogenetic protein (BMP) on osteoblast differentiation has been extensively investigated, its effect on osteoclast differentiation remains unknown. In the present study, in vitro effects of BMP-2 on osteoclast-like cell formation and bone resorption,were examined. BMP-2 (1-100 ng/ml) significantly stimulated bone resorption by preexistent osteoclast-like cells in mouse bone cell cultures containing stromal cells, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclast-like cells. When BMP-2 was added to unfractionated bone cells after degeneration of preexistent osteoclast-like cells, BMP-2, dose-dependently stimulated osteoclast-like cell formation at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3). Moreover, osteoclast-like cells newly formed by BMP-2 from unfractionated bone cells possessed the ability to form pits on dentine slices, Because these results indicated that BMP-2 directly or indirectly stimulated osteoclast differentiation and activity, we next examined the direct effect of BMP-2 on osteoclast precursors in the absence of stromal cells using hemopoietic blast cells derived from spleen cells. The mRNA for BMP-2/4 receptor was detected in hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as osteoblastic MC3T3-E1 cells and MC3T3-G2/PA6 stromal cells by RNase protection assay, BMP-2 dose-dependently stimulated osteoclast-like cell formation from hemopoietic blast cells supported by GM-CSF at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced 1,25(OH)(2)D-3-induced osteoclast-like cell formation from hemopoietic blast cells. The present data are the first to indicate that BMP-2 stimulates bone resorption through both direct stimulation of osteoclast formation and activation of mature osteoclasts, possibly via stromal cells, in vitro.