Effects of 6-Hydroxyflavone on Osteoblast Differentiation in MC3T3-E1 Cells

Chien-Hung Lai; Yu-Wei Wu; Shauh-Der Yeh; Yu-Hsaing Lin; Yu-Hui Tsai

doi:10.1155/2014/924560

Effects of 6-Hydroxyflavone on Osteoblast Differentiation in MC3T3-E1 Cells

Evid Based Complement Alternat Med. 2014:2014:924560. doi: 10.1155/2014/924560. Epub 2014 Mar 26.

Authors

Chien-Hung Lai¹, Yu-Wei Wu², Shauh-Der Yeh³, Yu-Hsaing Lin⁴, Yu-Hui Tsai⁵

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Graduate Institute of Medical Sciences, College of Medicine, TMU, No. 250, Wuxing Street, Taipei 11031, Taiwan.
⁵ 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.

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.