Kano J, Sugimoto T, Fukase M, Fujita T
Department of Medicine, Kobe University School of Medicine, Japan.
Biochem Biophys Res Commun. 1991 Aug 30;179(1):97-101. doi: 10.1016/0006-291x(91)91339-e.
The present study was performed to compare the effect of parathyroid hormone-related protein (PTHrP) on the proliferation of osteoblastic osteosarcoma cells (UMR-106) with that of PTH and characterize the direct involvement of cAMP in the change of osteoblast proliferation by PTHrP. Human(h)PTHrP-(1-34) (10(-11)-10(-7)M) dose-dependently inhibited [3H]thymidine incorporation (TdR) in the same manner as hPTH-(1-34). The simultaneous addition of PTHrP and PTH at a maximal effective dose of 10(-7) M did not cause additive suppressive effect on cell proliferation. Rp-cAMPs, which has been recently shown to act directly as antagonist in the activation of cAMP-dependent protein kinase (PKA), dose-dependently (10(-6)-10(-4)M) antagonized PTHrP-induced suppression of TdR in the same manner as PTH. Present study indicated that PTHrP has the same effect on osteoblast proliferation as PTH and that the activation of PKA is directly linked to the change of osteoblast proliferation by PTHrP.
本研究旨在比较甲状旁腺激素相关蛋白（PTHrP）与甲状旁腺激素（PTH）对成骨样骨肉瘤细胞（UMR-106）增殖的影响，并确定环磷酸腺苷（cAMP）在PTHrP引起的成骨细胞增殖变化中的直接作用。人（h）PTHrP-（1-34）（10^-11 - 10^-7 M）与hPTH-（1-34）一样，呈剂量依赖性抑制[3H]胸腺嘧啶核苷掺入（TdR）。以10^-7 M的最大有效剂量同时添加PTHrP和PTH，对细胞增殖并未产生相加性抑制作用。Rp-cAMPs最近被证明可直接作为环磷酸腺苷依赖性蛋白激酶（PKA）激活的拮抗剂，它与PTH一样，呈剂量依赖性（10^-6 - 10^-4 M）拮抗PTHrP诱导的TdR抑制。目前的研究表明，PTHrP对成骨细胞增殖的影响与PTH相同，且PKA的激活与PTHrP引起的成骨细胞增殖变化直接相关。
