Second messenger signaling of c‐fos gene induction by parathyroid hormone (PTH) and PTH‐related peptide in osteoblastic osteosarcoma cells: Its role in osteoblast proliferation and osteoclast‐like cell formation
Second messenger signaling of c‐fos gene induction by parathyroid hormone (PTH) and PTH‐related peptide in osteoblastic osteosarcoma cells: Its role in osteoblast proliferation and osteoclast‐like cell formation
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成骨细胞骨肉瘤细胞中甲状旁腺激素（PTH）和 PTH 相关肽诱导 c-fos 基因的第二信使信号：其在成骨细胞增殖和破骨细胞样细胞形成中的作用
DOI：
10.1002/jcp.1041610221
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发表时间：
1994
影响因子：
5.6
通讯作者：
Kazuo Chihara
中科院分区：
文献类型：
--
作者：
J. Kano;T. Sugimoto;M. Kanatani;Yasuo Kuroki;T. Tsukamoto;M. Fukase;Kazuo Chihara
本研究旨在阐明甲状旁腺激素（PTH）诱导的c-fos基因表达中的第二信使信号，表征c-fos基因参与PTH对成骨细胞增殖和功能以及破骨细胞样细胞形成的调节，并比较PTH与PTH相关肽（PTHrP）的这些作用。在成骨细胞骨肉瘤细胞UMR-106中，10 - 8 M的人（h）PTH-（1 - 34）和hPTHrP-（1 - 34）均诱导了类似程度的瞬时c-fos基因表达。N6，O2'-二丁酰腺苷3′，5′-环一磷酸（dbcAMP）以及腺苷环3′，5 ′-硫代磷酸的Sp-非对映异构体（Sp-cAMPS）（cAMP依赖性蛋白激酶（PKA）的激活剂）诱导弱的c-fos基因表达。PKA抑制剂环3′，5 ′-硫代磷酸腺苷（Rp-cAMPS）的Rp-非对映异构体几乎完全拮抗dbcAMP-和Sp-cAMPS-诱导的c-fos基因表达，但对PTH-和PTHrP诱导的表达无明显抑制作用。佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），蛋白激酶C（PKC）的激活剂，诱导c-fos基因的强烈表达，而4α-佛波醇12，13-二癸酸酯（4αPDD），不能激活PKC，和钙离子载体（A23187和离子霉素）没有。蛋白激酶C抑制剂（H-7，50 μM）完全阻断PTH和PTHrP对c-fos基因的表达。与c-fos mRNA互补的反义寡脱氧核苷酸（as-ODN）已被证明可抑制其mRNA翻译，与具有与as-ODN相同核苷酸但具有随机序列的对照寡脱氧核苷酸相比，1 μM的as-ODN可显著拮抗PTH-和PTHrP诱导的[3 H]胸苷掺入抑制和破骨细胞样细胞形成刺激，但不会增加碱性磷酸酶活性。本研究表明PKC系统参与PTH和PTHrP的c-fos基因表达，也表明c-fos基因参与PTH和PTHrP对骨细胞生理学的调节。© 1994 Wiley利斯公司
The present study was performed to clarify second messenger signaling in parathyroid hormone (PTH)‐induced c‐fos gene expression, to characterize the participation of the c‐fos gene in the regulation of osteoblast proliferation and function as well as osteoclast‐like cell formation by PTH and to compare these effects of PTH with those of PTH‐related peptide (PTHrP). Both human (h) PTH‐(1‐34) and hPTHrP‐(1‐34) at 10‐8 M induced a transient c‐fos gene expression to a similar degree in osteoblastic osteosarcoma cells, UMR‐106. N6, O2' ‐dibutyryl adenosine 3′, 5′‐cyclic monophosphate (dbcAMP) as well as Sp‐diastereoisomer of adenosine cyclic 3′,5′‐phosphorothioate (Sp‐cAMPS), an activator of cAMP‐dependent protein kinase (PKA), induced a weak c‐fos gene expression. Although Rp‐diastereoisomer of adenosine cyclic 3′,5′‐phosphorothioate (Rp‐cAMPS), an inhibitor of PKA, almost completely antagonized dbcAMP‐and Sp‐cAMPS‐induced expression of c‐fos gene, it did not cause an obvious inhibition of PTH‐or PTHrP‐induced expression. Phorbol 12‐myristate 13‐acetate (PMA), an activator of protein kinase C (PKC), induced an intense expression of the c‐fos gene, while 4α‐phorbol 12, 13‐didecanoate (4αPDD), incapable of activating PKC, and calcium ionophores (A23187 and ionomycin) did not. Protein kinase C inhibitor (H‐7, 50 μM) completely blocked the expression of the c‐fos gene by PTH as well as by PTHrP. Antisense oligodeoxynucleotides (as‐ODN) complementary to c‐fos mRNA, which have been shown to inhibit its mRNA translation, at 1 μM significantly antagonized PTH‐and PTHrP‐induced inhibition of [3H] thymidine incorporation and stimulation of osteoclast‐like cell formation in the presence of osteoblasts, but not an increase in alkaline phosphatase activity, compared to control oligodeoxynucleotides with same nucleotides as as‐ODN but with a random sequence. The present study indicates the involvement of PKC system in c‐fos gene expression by PTH as well as PTHrP and also indicates the involvement of the c‐fos gene in the regulation of bone cell physiology by PTH and PTHrP. © 1994 Wiley‐Liss, Inc.
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DOI：
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DOI：
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DOI：
10.1210/mend.6.11.1480173
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1992
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
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DOI：
10.1210/mend-3-2-232
发表时间：
1989
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
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