Pollock J H, Blaha M J, Lavish S A, Stevenson S, Greenfield E M
Department of Orthopaedics, Case Western Reserve University, Cleveland, Ohio, USA.
J Bone Miner Res. 1996 Jun;11(6):754-9. doi: 10.1002/jbmr.5650110606.
We have previously reported that parathyroid hormone (PTH) and PTH related protein (PTHrP) stimulate expression of interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) in osteoblasts in vitro. In the current study, we have developed a model of hormone injection into the subcutaneous space overlying mouse parietal bones to demonstrate that similar processes occur in osteoblasts in vivo. Specifically, PTH and PTHrP rapidly and transiently induce expression of the mRNAs encoding IL-6 and LIF. The effects are dose-dependent, with a maximal stimulation of approximately 50-fold for each cytokine. Although PTH and PTHrP activate both adenyl cyclase and phospholipase C-dependent signal transduction pathways, stimulation of IL-6 and LIF depends on adenyl cyclase since it is not reproduced by PTH(3-34), a partial agonist that only activates phospholipase C. These results confirm our previous in vitro studies and support the hypothesis that IL-6 and/or LIF are physiologically important mediators of at least some of the actions of PTH and PTHrP.
我们之前曾报道，甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP）在体外可刺激成骨细胞中白细胞介素-6（IL-6）和白血病抑制因子（LIF）的表达。在本研究中，我们建立了一种将激素注射到小鼠顶骨上方皮下空间的模型，以证明体内成骨细胞中也会发生类似过程。具体而言，PTH和PTHrP能快速且短暂地诱导编码IL-6和LIF的mRNA表达。这些作用具有剂量依赖性，每种细胞因子的最大刺激倍数约为50倍。尽管PTH和PTHrP可激活腺苷酸环化酶和磷脂酶C依赖性信号转导途径，但IL-6和LIF的刺激依赖于腺苷酸环化酶，因为仅激活磷脂酶C的部分激动剂PTH(3-34)无法产生这种刺激作用。这些结果证实了我们之前的体外研究，并支持以下假说：IL-6和/或LIF是PTH和PTHrP至少某些作用的重要生理介质。
