title: Effects of 6-Hydroxyflavone on Osteoblast Differentiation in MC3T3-E1 Cells.
abstract: Osteoblast differentiation plays an essential role in bone integrity. Isoflavones and some flavonoids are reported to have osteogenic activity and potentially possess the ability to treat osteoporosis. However, limited information concerning the osteogenic characteristics of hydroxyflavones is available. This study investigates the effects of various hydroxyflavones on osteoblast differentiation in MC3T3-E1 cells. The results showed that 6-hydroxyflavone (6-OH-F) and 7-hydroxyflavone (7-OH-F) stimulated ALP activity. However, baicalein and luteolin inhibited ALP activity and flavone showed no effect. Up to 50  μ M of each compound was used for cytotoxic effects study; flavone, 6-OH-F, and 7-OH-F had no cytotoxicity on MC3T3-E1 cells. Moreover, 6-OH-F activated AKT and serine/threonine kinases (also known as protein kinase B or PKB), extracellular signal-regulated kinases (ERK 1/2), and the c-Jun N-terminal kinase (JNK) signaling pathways. On the other hand, 7-OH-F promoted osteoblast differentiation mainly by activating ERK 1/ 2 signaling pathways. Finally, after 5 weeks of 6-OH-F induction, MC3T3-E1 cells showed a significant increase in the calcein staining intensity relative to merely visible mineralization observed in cells cultured in the osteogenic medium only. These results suggested that 6-OH-F could activate AKT, ERK 1/2, and JNK signaling pathways to effectively promote osteoblastic differentiation.
authors.affiliation: Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University (TMU), No. 250, Wuxing Street, Taipei 11031, Taiwan ; Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital (TMUH), No. 252, Wuxing Street, Taipei 11031, Taiwan ; International Institute of Nano Biomedicine, TMU, No. 252, Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Chien-Hung
authors.identifier: 0000-0002-5765-3120
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan ; Center for Teeth Bank and Dental Stem Cell Technology, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Department of Urology, School of Medicine, College of Medicine, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan ; Department of Urology, TMUH, No. 252, Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Shauh-Der
authors.initials: SD
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Yu-Hsaing
authors.initials: YH
authors.lastname: Lin
authors.affiliation: International Institute of Nano Biomedicine, TMU, No. 252, Wuxing Street, Taipei 11031, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan ; Center for Teeth Bank and Dental Stem Cell Technology, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Tsai