Nishiyama K, Sugimoto T, Kaji H, Kanatani M, Kobayashi T, Chihara K
Department of Medicine, Kobe University School of Medicine, Japan.
Endocrinology. 1996 Jan;137(1):35-41. doi: 10.1210/endo.137.1.8536635.
Although the actions of GH on osteoblasts have been extensively investigated, its effects on osteoclasts remain unknown. In the present study, the effects of GH on bone resorption and osteoclast differentiation were examined in vitro. Bovine GH (bGH; 1-100 ng/ml) significantly stimulated bone resorption by preexistent osteoclasts in stromal cell-containing mouse bone cell cultures, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclasts. When bGH was added to unfractionated bone cells after degeneration of preexistent osteoclasts, it concentration dependently stimulated osteoclast-like cell formation. GH also enhanced 1,25-dihydroxyvitamin D3-induced osteoclast-like cell formation. Moreover, osteoclast-like cells newly formed from unfractionated bone cells in the presence of bGH possessed the ability to form pits on dentine slices. The conditioned medium from osteoblastic MC3T3-E1 cells or MC3T3-G2/PA-6 stromal cells pretreated with bGH stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. On the other hand, the PCR products corresponding in size to the mouse GH receptor were detected in mouse hemopoietic blast cells as well as liver. GH concentration dependently stimulated osteoclast-like cell formation from these hemopoietic blast cells in the absence of stromal cells, and these osteoclast-like cells formed pits on dentine slices in the presence of MC3T3-G2/PA-6 stromal cells. The present study indicated for the first time that GH stimulates osteoclastic bone resorption through both its direct and indirect actions on osteoclast differentiation and through its indirect activation of mature osteoclasts, possibly via stromal cells, including osteoblasts.
尽管生长激素（GH）对成骨细胞的作用已得到广泛研究，但其对破骨细胞的影响仍不清楚。在本研究中，体外检测了GH对骨吸收和破骨细胞分化的影响。牛生长激素（bGH；1 - 100 ng/ml）显著刺激含基质细胞的小鼠骨细胞培养物中已有的破骨细胞进行骨吸收，而对分离的兔破骨细胞的骨吸收活性没有影响。当在已有的破骨细胞退化后将bGH添加到未分级的骨细胞中时，它以浓度依赖的方式刺激破骨细胞样细胞形成。GH还增强了1,25 - 二羟维生素D3诱导的破骨细胞样细胞形成。此外，在bGH存在下从未分级的骨细胞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。用bGH预处理的成骨细胞MC3T3 - E1细胞或MC3T3 - G2/PA - 6基质细胞的条件培养基刺激由粒细胞 - 巨噬细胞集落刺激因子支持的小鼠造血母细胞形成破骨细胞样细胞。另一方面，在小鼠造血母细胞以及肝脏中检测到大小与小鼠GH受体相对应的PCR产物。在没有基质细胞的情况下，GH以浓度依赖的方式刺激这些造血母细胞形成破骨细胞样细胞，并且这些破骨细胞样细胞在MC3T3 - G2/PA - 6基质细胞存在下在牙本质切片上形成凹坑。本研究首次表明，GH通过其对破骨细胞分化的直接和间接作用以及通过其对成熟破骨细胞的间接激活（可能通过包括成骨细胞在内的基质细胞）来刺激破骨细胞性骨吸收。
