Benzo[a]pyrene Regulates Osteoblast Proliferation through an Estrogen Receptor-Related Cyclooxygenase-2 Pathway
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- 作者：Keh Sung Tsai ; Rong Sen Yang ; and Shing Hwa Liu
- 刊名：Chemical Research in Toxicology
- 出版年：2004
- 出版时间：May 2004
- 年：2004
- 卷：17
- 期：5
- 页码：679 - 684
- 全文大小：121K
- 年卷期：v.17,no.5(May 2004)
- ISSN：1520-5010
文摘
Polycyclic aromatic hydrocarbons (PAHs) have been known as a kind of xenoestrogen. Benzo[a]pyrene, a PAH present in tobacco smoke and tar, has been implicated in the induction ofcell proliferation as well as tumors including osteosarcoma. Nevertheless, the literature aboutthe action of benzo[a]pyrene on the bone system is rare. It has been identified that osteoblastsowned the estrogen receptors and estrogen could modulate the osteoblast proliferation. In thisstudy, we found that benzo[a]pyrene was capable of increasing the cell proliferation in culturedrat osteoblasts, human osteosarcoma cell line (MG-63), and estrogen sensitive human cell line(MCF-7) but not in the human estrogen receptor negative cell line (MDA-MB-231). This benzo[a]pyrene-induced osteoblast proliferation could be inhibited by the estrogen receptor antagonistICI182780 and tamoxifen, PD98059 [extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor], and LY294002 [phosphatidylinositol 3-kinase(PI3K) inhibitor] but not 
-naphthoflavone (aryl hydrocarbon receptor antagonist) andSB203580 (p38 MAPK inhibitor). Western blot analysis showed that benzo[a]pyrene couldinduce the phosphorylation of ERK1/2 and Akt (PI3K downstream effector) in osteoblasts. Theproliferating cell nuclear antigen protein levels in nuclear fraction of osteoblasts were alsoincreased by benzo[a]pyrene. Moreover, cyclooxygenase-2 (COX-2), but not COX-1, expressioncould be induced in osteoblasts under benzo[a]pyrene treatment. Its upregulation was associatedwith the induction of prostaglandin E2 (PGE2). COX-2 inhibitors NS398 and aspirin are capableof inhibiting the benzo[a]pyrene-induced osteoblast proliferation. These results indicate thatbenzo[a]pyrene may modulate the osteoblast proliferation through activation of COX-2 protein.
-naphthoflavone (aryl hydrocarbon receptor antagonist) andSB203580 (p38 MAPK inhibitor). Western blot analysis showed that benzo[a]pyrene couldinduce the phosphorylation of ERK1/2 and Akt (PI3K downstream effector) in osteoblasts. Theproliferating cell nuclear antigen protein levels in nuclear fraction of osteoblasts were alsoincreased by benzo[a]pyrene. Moreover, cyclooxygenase-2 (COX-2), but not COX-1, expressioncould be induced in osteoblasts under benzo[a]pyrene treatment. Its upregulation was associatedwith the induction of prostaglandin E2 (PGE2). COX-2 inhibitors NS398 and aspirin are capableof inhibiting the benzo[a]pyrene-induced osteoblast proliferation. These results indicate thatbenzo[a]pyrene may modulate the osteoblast proliferation through activation of COX-2 protein.