Linkhart T A, Keffer M J
Department of Biochemistry, Loma Linda University School of Medicine, California.
Endocrinology. 1991 Mar;128(3):1511-8. doi: 10.1210/endo-128-3-1511.
In a previous study we found that PTH stimulated bone resorption and release of insulin-like growth factor-I (IGF-I) and IGF-II from cultured neonatal mouse calvaria. Since IGF-I and IGF-II stimulate osteoblast proliferation and collagen synthesis, these results suggested that increased release of IGFs during resorption could mediate in part coupling of bone formation to bone resorption. In the present study two other osteolytic agents, transforming growth factor-beta (TGF beta) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 were examined for effects on IGF release from neonatal mouse calvaria. Like PTH, TGF beta stimulated resorption and increased release of IGF-I and IGF-II. 1,25-(OH)2D3, however, stimulated resorption and IGF-II release comparable to PTH, but inhibited release of IGF-I. 1,25-(OH)2D3 (0.1-100 nM) inhibited basal release of IGF-I, and 10 nM 1,25-(OH)2D3 inhibited release of IGF-I induced by PTH or TGF beta. The effects of 1,25-(OH)2D3 were specific to this vitamin D metabolite and did not occur with 25-hydroxyvitamin D3 or 24,25-(OH)2D3 at the same concentration. Calcitonin (50 mU/ml) decreased 1,25-(OH)2D3 stimulation of resorption, but did not affect 1,25-(OH)2D3 stimulation of IGF-II release and inhibition of IGF-I release. This evidence that effects of 1,25-(OH)2D3 on release of the IGFs were independent of bone resorption supports the conclusion that 1,25-(OH)2D3 modulated the production and secretion of IGF-I and IGF-II in calvarial cells. The results of this and the previous study suggest that PTH, TGF beta, and 1,25-(OH)2D3 differentially regulate mouse calvarial cell IGF-I and IGF-II production.
在之前的一项研究中，我们发现甲状旁腺激素（PTH）可刺激骨吸收，并促使胰岛素样生长因子-I（IGF-I）和胰岛素样生长因子-II（IGF-II）从培养的新生小鼠颅骨中释放出来。由于IGF-I和IGF-II可刺激成骨细胞增殖和胶原蛋白合成，这些结果表明，在骨吸收过程中IGF释放的增加可能部分介导了骨形成与骨吸收的偶联。在本研究中，我们检测了另外两种溶骨剂——转化生长因子-β（TGF-β）和1,25-二羟基维生素D3 [1,25-(OH)2D3] 对新生小鼠颅骨IGF释放的影响。与PTH一样，TGF-β刺激了骨吸收，并增加了IGF-I和IGF-II的释放。然而，1,25-(OH)2D3刺激骨吸收和IGF-II释放的程度与PTH相当，但抑制了IGF-I的释放。1,25-(OH)2D3（0.1 - 100 nM）抑制了IGF-I的基础释放，10 nM的1,25-(OH)2D3抑制了由PTH或TGF-β诱导的IGF-I释放。1,25-(OH)2D3的作用对这种维生素D代谢产物具有特异性，相同浓度的25-羟基维生素D3或24,25-(OH)2D3则不会出现这种情况。降钙素（50 mU/ml）降低了1,25-(OH)2D3对骨吸收的刺激作用，但不影响1,25-(OH)2D3对IGF-II释放的刺激作用以及对IGF-I释放的抑制作用。这一证据表明，1,25-(OH)2D3对IGF释放的影响独立于骨吸收，支持了1,25-(OH)2D3调节颅骨细胞中IGF-I和IGF-II的产生和分泌这一结论。本研究及之前研究的结果表明，PTH、TGF-β和1,25-(OH)2D3对小鼠颅骨细胞IGF-I和IGF-II的产生具有不同的调节作用。
