Flavonoids, a group of natural compounds found in a variety of vegetables and herbal medicines, are well known to possess diverse biological effects. They are structurally very similar to estrogen and many of them display strong estrogen-liked activities, which have been used as the alternatives of estrogen. Recent researches have been intensively reported on their ability to affect bone metabolism. In particular, a study carried out on a group of post-menopausal women has supported that dietary flavonoid intakes are associated with bone health. In order to obtain a further understanding of the beneficial effects of flavonoids on bone health, different sub-classes of flavonoids were screened for their ability to influence bone differentiation in the present study. The osteogenic effects...[ Read more ]

Flavonoids, a group of natural compounds found in a variety of vegetables and herbal medicines, are well known to possess diverse biological effects. They are structurally very similar to estrogen and many of them display strong estrogen-liked activities, which have been used as the alternatives of estrogen. Recent researches have been intensively reported on their ability to affect bone metabolism. In particular, a study carried out on a group of post-menopausal women has supported that dietary flavonoid intakes are associated with bone health. In order to obtain a further understanding of the beneficial effects of flavonoids on bone health, different sub-classes of flavonoids were screened for their ability to influence bone differentiation in the present study. The osteogenic effects of these flavonoids were first determined by measuring alkaline phosphatase (ALP) activity in cultured rat osteoblasts. The potential flavonoids were then chosen for further mechanistic studies in order to reveal the possible signaling cascades in mediating their osteogenic effects. In cultured osteoblasts, application of potential flavonoids increased significantly the osteoblastic differentiation and the levels of mRNAs encoding the bone differentiation markers, including osteonectin, osteocalcin and collagen type 1 α 1.

The flavonol kaempferol derived from Kaempferia galange, was shown to exert its osteogenic effect via the activation of the classical estrogen receptor (ER) signaling, including the induction of ERα phosphorylation and the transcriptional activation of the estrogen responsive element (ERE). On the other hand, the osteogenic effect of baicalin, a flavone derived mainly from the roots of Scutellaria baicalensis was showed to be independent to its estrogenic activity. Baicalin promoted osteoblastic differentiation via the activation of Wnt/β-catenin signaling pathway: the activation resulted in the phosphorylation of glycogen synthase kinase 3 β (GSK3β) and, subsequently, induced the nuclear accumulation of the β-catenin, leading to the transcription activation of Wnt-targeted genes for osteogenesis. The baicalin-induced osteogenic effects were fully abolished by DKK-1, a blocker of Wnt/β-catenin receptor. Moreover, baicalin also enhanced the mRNA expression of osteoprotegerin (OPG), which could regulate indirectly the activation of osteoclasts.

In addition to the well-known osteogenic pathways, a novel osteogenic pathway that is mediated by a cholinergic enzyme, acetylcholinesterase (AChE) was also revealed here, as another possible mechanism in mediating the flavonoid-induced osteogenesis. AChE is commonly known for its cholinergic function in neurotransmission. Recent findings suggested that AChE is also involved in bone differentiation. In culture osteoblasts, PRiMA (p̲roline r̲ich m̲embrane a̲nchor)-linked AChE was detected as the major form of enzyme. The expression of PRiMA and AChE mRNAs were stimulated during osteoblast differentiation. The bone mineral density of AChE^-/- mice is reduced, and a slower bone formation rate was also recorded, implicating that AChE mediation can be one of the possible mechanisms of flavonoids for their osteogenic properties.

Taken together, our studies on the possible mechanisms that mediating the flavonoid-induced osteogenic effects is of great importance for the development of better therapeutic options for osteoporosis, and that the identifications of these osteogenic flavonoids could be very useful in developing potential drugs, or food supplements, for treating the metabolic bone disease.