TY - JOUR
T1 - Melatonin delays cell proliferation by inducing G1 and G 2/M phase arrest in a human osteoblastic cell line hFOB 1.19
AU - Liu, Lifeng
AU - Zhu, Yue
AU - Xu, Ying
AU - Reiter, Russel J.
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Abstract: A recent prospective study indicated that melatonin supplements may reduce the progression of idiopathic scoliosis, the most common deformity of the spine. This form of scoliosis occurs during rapid skeletal growth. To date, however, there is no direct evidence regarding an antiproliferative effect of melatonin at the level of osteoblasts. Herein, we investigated whether melatonin inhibits cell proliferation in a normal human fetal osteoblastic cell line hFOB 1.19. MTT staining showed that at 1 mm concentrations, melatonin significantly inhibited osteoblast proliferation in time-dependent manner. Flow cytometry demonstrated that melatonin significantly increased the fraction of cells in G0/G1 phase of the cell cycle, while simultaneously reducing the proportion in the G2/M phase rather than the S phase. Western blot and real-time PCR analyses further confirmed that melatonins inhibitory effect was possibly because of downregulation of cyclin D1 and CDK4, related to the G1 phase, and of cyclin B1 and CDK1, related to the G2/M phase. There was no downregulation of cyclin E, CDK2, and cyclin A, which are related to G1/S transition and S phase. In addition, the trypan blue dye exclusion assay showed that cell viability was not changed by melatonin relative to control cells. These findings provide evidence that melatonin may significantly delay osteoblast proliferation in a time-dependent manner and this inhibition involves the downregulation of cyclin D1 and CDK4, related to the G1 phase, and of cyclin B1 and CDK1, related to the G2/M phase.
AB - Abstract: A recent prospective study indicated that melatonin supplements may reduce the progression of idiopathic scoliosis, the most common deformity of the spine. This form of scoliosis occurs during rapid skeletal growth. To date, however, there is no direct evidence regarding an antiproliferative effect of melatonin at the level of osteoblasts. Herein, we investigated whether melatonin inhibits cell proliferation in a normal human fetal osteoblastic cell line hFOB 1.19. MTT staining showed that at 1 mm concentrations, melatonin significantly inhibited osteoblast proliferation in time-dependent manner. Flow cytometry demonstrated that melatonin significantly increased the fraction of cells in G0/G1 phase of the cell cycle, while simultaneously reducing the proportion in the G2/M phase rather than the S phase. Western blot and real-time PCR analyses further confirmed that melatonins inhibitory effect was possibly because of downregulation of cyclin D1 and CDK4, related to the G1 phase, and of cyclin B1 and CDK1, related to the G2/M phase. There was no downregulation of cyclin E, CDK2, and cyclin A, which are related to G1/S transition and S phase. In addition, the trypan blue dye exclusion assay showed that cell viability was not changed by melatonin relative to control cells. These findings provide evidence that melatonin may significantly delay osteoblast proliferation in a time-dependent manner and this inhibition involves the downregulation of cyclin D1 and CDK4, related to the G1 phase, and of cyclin B1 and CDK1, related to the G2/M phase.
KW - cell cycle
KW - human
KW - melatonin
KW - osteoblast
KW - proliferation
KW - scoliosis
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U2 - 10.1111/j.1600-079X.2010.00832.x
DO - 10.1111/j.1600-079X.2010.00832.x
M3 - Article
C2 - 21108658
AN - SCOPUS:79951633128
VL - 50
SP - 222
EP - 231
JO - Journal of Pineal Research
JF - Journal of Pineal Research
SN - 0742-3098
IS - 2
ER -