Chihara K, Sugimoto T
Department of Medicine, Kobe University School of Medicine, Japan.
Horm Res. 1997;48 Suppl 5:45-9. doi: 10.1159/000191328.
Bone remodelling is a cyclical phenomenon consisting of osteoclastic bone resorption followed by osteoblastic bone formation. Although recent evidence suggests that GH participates in bone remodelling, the exact mechanism remains unclear. The present series of in vitro studies aimed to clarify how GH affects bone formation and resorption. GH binding sites were found to be present in osteoblastic MC3T3-E1 cells. Bovine GH (bGH) increased DNA synthesis, stimulated alkaline phosphatase activity and enhanced both type I procollagen mRNA expression and collagen synthesis. GH also increased the expression of both IGF-I and IGF-binding protein-5 mRNA as well as the release of IGF-I from these cells. The addition of IGF-I or recombinant IGFBP-5 alone significantly increased ALP activity and type I procollagen mRNA expression. These findings indicate that GH acts directly on osteoblasts to stimulate bone formation and that IGF-I and IGFBP-5 are involved in GH-stimulated bone formation. GH also stimulated pit formation on dentine slices and osteoclast differentiation in stromal cell-containing mouse bone cell cultures, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The addition of IGF-I or rIGFBP-5 alone exhibited similar effects. These stimulatory effects of GH on pit formation and osteoclast differentiation were significantly blocked in the presence of neutralizing anti-IGF-I antibody. PCR products corresponding in size to the mouse GH receptor were detected in osteoclast precursor cells. GH stimulated osteoclast-like cell formation from these 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. These findings indicate that GH stimulates osteoclastic bone resorption through both its direct and indirect action on the maturation of osteoclast precursor cells and through its indirect activation of mature osteoclasts, possibly via stromal cells. In conclusion, GH stimulates osteoclastic bone resorption as well as osteoblastic bone formation in vitro, and locally produced IGF-I and/or IGFBP-5 are involved in the stimulation of bone remodelling by GH.
骨重塑是一种周期性现象，包括破骨细胞介导的骨吸收，随后是成骨细胞介导的骨形成。尽管最近的证据表明生长激素（GH）参与骨重塑，但其确切机制仍不清楚。本系列体外研究旨在阐明GH如何影响骨形成和骨吸收。研究发现成骨细胞MC3T3-E1细胞中存在GH结合位点。牛生长激素（bGH）可增加DNA合成，刺激碱性磷酸酶活性，并增强I型前胶原mRNA表达和胶原蛋白合成。GH还可增加IGF-I和IGF结合蛋白-5 mRNA的表达以及这些细胞中IGF-I的释放。单独添加IGF-I或重组IGFBP-5可显著增加碱性磷酸酶活性和I型前胶原mRNA表达。这些发现表明，GH直接作用于成骨细胞以刺激骨形成，并且IGF-I和IGFBP-5参与GH刺激的骨形成。GH还可刺激含基质细胞的小鼠骨细胞培养物中牙本质切片上的陷窝形成和破骨细胞分化，而对分离的兔破骨细胞的骨吸收活性没有影响。单独添加IGF-I或rIGFBP-5也表现出类似的效果。在存在中和抗IGF-I抗体的情况下，GH对陷窝形成和破骨细胞分化的这些刺激作用被显著阻断。在破骨细胞前体细胞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可刺激这些细胞形成破骨细胞样细胞，并且这些破骨细胞样细胞在存在MC3T3-G2/PA-6基质细胞的情况下在牙本质切片上形成陷窝。这些发现表明，GH通过对破骨细胞前体细胞成熟的直接和间接作用以及通过对成熟破骨细胞的间接激活（可能通过基质细胞）来刺激破骨细胞介导的骨吸收。总之，GH在体外可刺激破骨细胞介导的骨吸收以及成骨细胞介导的骨形成，并且局部产生的IGF-I和/或IGFBP-5参与GH对骨重塑的刺激作用。
