Mochizuki H, Hakeda Y, Wakatsuki N, Usui N, Akashi S, Sato T, Tanaka K, Kumegawa M
Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, Japan.
Endocrinology. 1992 Sep;131(3):1075-80. doi: 10.1210/endo.131.3.1505451.
Although the action of insulin-like growth factor-I (IGF-I) on bone formation has been extensively investigated, the effect of the factor on bone resorption is little known. We first examined the effect of IGF-I on bone resorption by preexistent osteoclasts by using unfractionated bone cells cultured on dentin slices. IGF-I had a dose-related effect of stimulating bone resorption by preexistent osteoclasts, whereas IGF-II did not. When IGF-I was added to cultures of bone cells after preexistent osteoclasts had degenerated on the dentin slices, IGF-I increased the number of osteoclastic multinucleate cells (MNCs) with tartrate-resistant acid phosphatase activity. Moreover, IGF-I augmented the area of pits produced by newly formed osteoclasts. These results suggest that IGF-I directly or indirectly stimulates osteoclast recruitment and activation. Therefore, we next examined the direct effect of IGF-I on osteoclastic MNC formation by using hemopoietic blast cells. In the presence of 1,25-dihydroxyvitamin D3, IGF-I, like granulocyte-macrophage colony-stimulating factor (GM-CSF), dose-dependently increased the number of TRAP-positive MNCs. This stimulatory effect of IGF-I was additive with that of GM-CSF. Both IGF-I and GM-CSF supported the survival of the blast cells, indicating that IGF-I as well as GM-CSF are supporting factors for osteoclast differentiation. In addition, the blast cells possessed high affinity binding sites for IGF-I, with a Kd of 0.8 nM. These data, thus, indicate that IGF-I stimulates osteoclastic bone resorption through its direct or indirect action of supporting the generation and activation of osteoclasts.
尽管胰岛素样生长因子-I（IGF-I）对骨形成的作用已得到广泛研究，但该因子对骨吸收的影响却鲜为人知。我们首先通过使用在牙本质切片上培养的未分离骨细胞，研究了IGF-I对已存在破骨细胞的骨吸收作用。IGF-I对已存在破骨细胞的骨吸收具有剂量相关的刺激作用，而IGF-II则没有。当在牙本质切片上已存在的破骨细胞退化后，将IGF-I添加到骨细胞培养物中时，IGF-I增加了具有抗酒石酸酸性磷酸酶活性的破骨细胞多核细胞（MNCs）的数量。此外，IGF-I增大了新形成破骨细胞产生的凹陷面积。这些结果表明，IGF-I直接或间接刺激破骨细胞的募集和激活。因此，我们接下来通过使用造血母细胞研究了IGF-I对破骨细胞MNC形成的直接作用。在1,25-二羟基维生素D3存在的情况下，IGF-I与粒细胞-巨噬细胞集落刺激因子（GM-CSF）一样，剂量依赖性地增加了TRAP阳性MNCs的数量。IGF-I的这种刺激作用与GM-CSF的刺激作用具有加和性。IGF-I和GM-CSF都支持母细胞的存活，表明IGF-I以及GM-CSF都是破骨细胞分化的支持因子。此外，母细胞具有高亲和力的IGF-I结合位点，解离常数（Kd）为0.8 nM。因此，这些数据表明，IGF-I通过其支持破骨细胞生成和激活的直接或间接作用来刺激破骨细胞性骨吸收。
