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2017 ; 9
(6
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Osthole Enhances Osteogenesis in Osteoblasts by Elevating Transcription Factor
Osterix via cAMP/CREB Signaling In Vitro and In Vivo
#MMPMID28629115
Zhang ZR
; Leung WN
; Li G
; Kong SK
; Lu X
; Wong YM
; Chan CW
Nutrients
2017[Jun]; 9
(6
): ä PMID28629115
show ga
Anabolic anti-osteoporotic agents are desirable for treatment and prevention of
osteoporosis and fragility fractures. Osthole is a coumarin derivative extracted
from the medicinal herbs Cnidium monnieri (L.) Cusson and Angelica pubescens
Maxim.f. Osthole has been reported with osteogenic and anti-osteoporotic
properties, whereas the underlying mechanism of its benefit still remains
unclear. The objective of the present study was to investigate the osteopromotive
action of osthole on mouse osteoblastic MC3T3-E1 cells and on mouse femoral
fracture repair, and to explore the interaction between osthole-induced
osteopromotive effect and cyclic adenosine monophosphate (cAMP) elevating effect.
Osthole treatment promoted osteogenesis in osteoblasts by enhancing alkaline
phosphatase (ALP) activity and mineralization. Oral gavage of osthole enhanced
fracture repair and increased bone strength. Mechanistic study showed osthole
triggered the cAMP/CREB pathway through the elevation of the intracellular cAMP
level and activation of the phosphorylation of the cAMP response element-binding
protein (CREB). Blockage of cAMP/CREB downstream signals with protein kinase A
(PKA) inhibitor KT5720 partially suppressed osthole-mediated osteogenesis by
inhibiting the elevation of transcription factor, osterix. In conclusion, osthole
shows osteopromotive effect on osteoblasts in vitro and in vivo. Osthole-mediated
osteogenesis is related to activation of the cAMP/CREB signaling pathway and
downstream osterix expression.