Nicotine induces cell proliferation in association with cyclin D1 up-regulation and inhibits cell differentiation in association with p53 regulation in a murine pre-osteoblastic cell line.
Recent studies have suggested that nicotine critically affects bone metabolism. Many studies have examined the effects of nicotine on proliferation and differentiation, but the underlying molecular mechanisms remain unclear. We examined cell cycle regulators involved in the proliferation and differentiation of MC3T3-E1 cells. Nicotine induced cell proliferation in association with p53 down-regulation and cyclin D1 up-regulation. In differentiated cells, nicotine reduced alkaline phosphatase activity and mineralized nodule formation in dose-dependent manners. Furthermore, p53 expression was sustained in nicotine-treated cells during differentiation. These findings indicate that nicotine promotes the cell cycle and inhibits differentiation in association with p53 regulation in pre-osteoblastic cells.
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama, Japan. tsato@saitama-med.ac.jp
Tsuyoshi
T
Sato
Takahiro
T
Abe
Norimichi
N
Nakamoto
Yasuhisa
Y
Tomaru
Noboru
N
Koshikiya
Junya
J
Nojima
Shoichiro
S
Kokabu
Yasuaki
Y
Sakata
Akio
A
Kobayashi
Tetsuya
T
Yoda
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism*; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
D011978:Receptors, Nicotinic; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D009538:Nicotine