Hakeda Y, Harada S, Matsumoto T, Tezuka K, Higashino K, Kodama H, Hashimoto-Goto T, Ogata E, Kumegawa M
Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, Japan.
J Biol Chem. 1991 Nov 5;266(31):21044-50.
Prostaglandin F2 alpha (PGF2 alpha) stimulates proliferation of clonal osteoblastic MC3T3-E1 cells mainly via the stimulation of phospholipase C. These cells constitutively produced and secreted insulin-like growth factor I (IGF-I). In addition, a neutralizing anti-IGF-I antibody completely abolished DNA synthesis stimulated by PGF2 alpha in MC3T3-E1 cells, suggesting that IGF-I indeed mediates the PGF2 alpha effect. However, PGF2 alpha decreased the expression of IGF-I mRNA and the secretion of immunoreactive IGF-I into the medium, whereas progression activity in the conditioned medium was not affected by PGF2 alpha. Although IGF-I alone did not stimulate DNA synthesis in MC3T3-E1 cells, when PGF2 alpha was added to the cultures, IGF-I stimulated their proliferation. Thus, PGF2 alpha may potentiate the action of IGF-I. At the same time, PGF2 alpha increased the number of high affinity binding sites (molecular mass of 130 kDa) for IGF-I in a dose-dependent manner. The increase in IGF-I-binding site number preceded the elevation of DNA synthesis by approximately 3 h. Furthermore, MC3T3-E1 cells secreted at least three species of IGF-binding proteins (IGFBPs) with molecular masses of 24, 30, and 34 kDa. In the early period of PGF2 alpha exposure, PGF2 alpha attenuated the secretion of all of these IGFBPs, whereas thereafter, it markedly increased their secretion, especially that of the 34-kDa IGFBP, suggesting a modulation of metabolism and action of IGF-I. These effects of PGF2 alpha on IGF-I receptor number and IGFBP secretion may play a role in the synergism between PGF2 alpha and IGF-I that results in the stimulation of DNA synthesis in MC3T3-E1 cells.
前列腺素F2α（PGF2α）主要通过刺激磷脂酶C来促进克隆性成骨MC3T3-E1细胞的增殖。这些细胞组成性地产生并分泌胰岛素样生长因子I（IGF-I）。此外，一种中和性抗IGF-I抗体完全消除了PGF2α刺激的MC3T3-E1细胞中的DNA合成，这表明IGF-I确实介导了PGF2α的作用。然而，PGF2α降低了IGF-I mRNA的表达以及免疫反应性IGF-I向培养基中的分泌，而条件培养基中的促增殖活性不受PGF2α影响。虽然单独的IGF-I不会刺激MC3T3-E1细胞中的DNA合成，但当向培养物中添加PGF2α时，IGF-I会刺激它们的增殖。因此，PGF2α可能增强IGF-I的作用。同时，PGF2α以剂量依赖性方式增加了IGF-I的高亲和力结合位点（分子量为130 kDa）的数量。IGF-I结合位点数量的增加比DNA合成的升高提前约3小时。此外，MC3T3-E1细胞分泌至少三种分子量分别为24、30和34 kDa的IGF结合蛋白（IGFBPs）。在PGF2α暴露的早期，PGF2α减弱了所有这些IGFBPs的分泌，而此后，它显著增加了它们的分泌，尤其是34-kDa IGFBP的分泌，这表明对IGF-I的代谢和作用有调节作用。PGF2α对IGF-I受体数量和IGFBP分泌的这些影响可能在PGF2α和IGF-I之间的协同作用中发挥作用，这种协同作用导致了MC3T3-E1细胞中DNA合成的刺激。
