Reppe Sjur, Olstad Ole K, Rian Edith, Gautvik Vigdis T, Gautvik Kaare M, Jemtland Rune
Department of Medical Biochemistry, University of Oslo, Oslo, Norway.
Biochem Biophys Res Commun. 2004 Nov 5;324(1):218-23. doi: 10.1016/j.bbrc.2004.09.030.
Parathyroid hormone (PTH) exerts potent and diverse effects in bone and cartilage through activation of type 1 PTH receptors (PTH1R) capable of coupling to protein kinase A (PKA) and PKC. We have used macroarrays to identify zinc finger protein butyrate response factor-1 (BRF1) as a novel PTH regulated gene in clonal and normal osteoblasts of human and rodent origin. We further demonstrate that in human osteoblast-like OHS cells, biologically active hPTH(1-84) and hPTH(1-34) stimulate BRF1 mRNA expression in a dose- and time-dependent manner, while the amino-terminally truncated hPTH(3-84) which does not activate PTH1R has no effect. Moreover, using specific stimulators or inhibitors of PKA and PKC activity, the PTH-elicited BRF1 mRNA expression is mediated through the PKA signaling pathway. In mouse calvarial osteoblasts, BRF1 mRNA levels are upregulated by PTH(1-84) and reduced in response to bone morphogenetic protein 2 (BMP-2). Hence, our data showing that BRF1 is expressed in osteoblastic cells and regulated by PTH and BMP-2, suggest an important role for BRF1 in osteoblasts within the molecular network of PTH-dependent bone remodeling.
甲状旁腺激素（PTH）通过激活能够与蛋白激酶A（PKA）和蛋白激酶C（PKC）偶联的1型PTH受体（PTH1R），在骨骼和软骨中发挥强大而多样的作用。我们利用基因芯片，在人和啮齿动物来源的克隆和成骨细胞中，鉴定出锌指蛋白丁酸盐反应因子-1（BRF1）是一种新的PTH调控基因。我们进一步证明，在人成骨样OHS细胞中，具有生物活性的hPTH(1-84)和hPTH(1-34)以剂量和时间依赖性方式刺激BRF1 mRNA表达，而不激活PTH1R的氨基末端截短型hPTH(3-84)则无作用。此外，使用PKA和PKC活性的特异性刺激剂或抑制剂，PTH诱导的BRF1 mRNA表达是通过PKA信号通路介导的。在小鼠颅骨成骨细胞中，BRF1 mRNA水平被PTH(1-84)上调，并对骨形态发生蛋白2（BMP-2）产生反应而降低。因此，我们的数据表明BRF1在成骨细胞中表达，并受PTH和BMP-2调控，这表明BRF1在PTH依赖性骨重塑分子网络中的成骨细胞中具有重要作用。
