Bone Morphogenetic Protein-2 and -4 (BMP-2 and -4) Mediates Fraxetin-Induced Maturation and Differentiation in Human Osteoblast-Like Cell Lines

Kuo, Po‐Lin; Huang, Yu‐Ting; Chang, Chih‐Hao; Chang, Jiunn-Kae

doi:10.1248/bpb.29.119

Cited by 25 publications

(16 citation statements)

References 37 publications

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“…Several natural or chemical compounds have been reported to induce osteoblast differentiation by induction of BMPs and/or Smad signaling, such as osthole, fraxetin, and myricetin (Kuo et al, 2005(Kuo et al, , 2006Hsu et al, 2007). The present results indicated that BMP-2 mediates 8-PK-induced maturation and differentiation in MC3T3-E1 cells.…”

Section: Involvement Of Runx2 In 8-pk-induced Osteoblast Differentiationsupporting

confidence: 58%

8-Prenylkaempferol accelerates osteoblast maturation through bone morphogenetic protein-2/p38 pathway to activate Runx2 transcription

Chiou

Lee²,

Liao³

et al. 2011

Life Sciences

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Section: Involvement Of Runx2 In 8-pk-induced Osteoblast Differentiationsupporting

confidence: 58%

8-Prenylkaempferol accelerates osteoblast maturation through bone morphogenetic protein-2/p38 pathway to activate Runx2 transcription

Chiou

Lee²,

Liao³

et al. 2011

Life Sciences

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“…BMP-2 expression in osteoblasts promotes cell maturation and differentiation [40] . As we and others have shown, CGRP increases BMP-2 expression in osteoblasts [41] .…”

Section: Discussionmentioning

confidence: 99%

Calcitonin gene-related peptide stimulates BMP-2 expression and the differentiation of human osteoblast-like cells in vitro

2013

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Aim: To investigate whether bone morphogenic protein-2 (BMP-2) expression was involved in calcitonin gene-related peptide (CGRP)-induced osteogenesis in human osteoblast-like cells in vitro. Methods: MG-63 osteogenic human osteosarcoma cells were treated with CGRP (10 -8 mol/L) for 48 h. Cell cycle phases were determined using flow cytometry assay. The protein levels of BMP-2, ALP, Osteocalcin, ColIa1, CREB, and pCREB were measured with Western blotting, while the mRNA level of BMP-2 was measured with qR-T PCR. The expression of ALP in MG-63 cells was also studied using immunofluorescence staining. The level of cAMP was measured with ELISA assay. Results: CGRP treatment significantly stimulated proliferation of MG-63 cells, and increased the expression of BMP-2 and the osteogenic proteins ALP, Osteocalcin and ColIa1. Pretreatment with the BMP signaling inhibitor Noggin (100 ng/mL) did not affect CGRPstimulated proliferation and BMP-2 expression, but abolished the CGRP-induced increases of the osteogenic proteins ALP, Osteocalcin and ColIa1. Furthermore, CGRP treatment markedly increased cAMP level in MG-63 cells, whereas pretreatment with the cAMP pathway inhibitor H89 (5 μmol/L) abolished the CGRP-induced increases of cAMP level and BMP-2 expression. Conclusion: In MG-63 cells, the BMP pathway is involved in CGRP-induced osteogenic differentiation but not in proliferation, whereas the cAMP/pCREB pathway is involved in the expression of BMP-2.Keywords: c calcitonin gene-related peptide; Noggin; H89; MG-63 human osteosarcoma cell; osteogenesis; bone morphogenic protein; cAMP/pCREB pathway Acta Pharmacologica Sinica (2013Sinica ( ) 34: 1467Sinica ( -1474 doi: 10.1038/aps.2013 published online 27 May 2013 Original Article IntroductionSensory nerve activation has a centrally mediated but poorly understood action on bone. The relative importance and interactions between autonomic, sensory, and peripheral nervous system actions on bone mass are not clear in healthy individuals and even less so in pathologic states. Understanding how the central nervous system integrates homeostatic signals with the regulation of bone homeostasis is an exciting research area.Experimental evidence suggests that the nervous system is involved in bone remodeling. In response to fracture or other trauma, peripheral peptidergic neurons can influence osteoclast formation through the production of several neuropeptides. Calcitonin gene-related peptide (CGRP), a 37-residue peptide generated in specific neurons by alternative splicing of the calcitonin gene, is an important neuropeptide expressed * To whom correspondence should be addressed.E-mail tanyhoms@yahoo.cn Received 2012-10-30 Accepted 2013-03-25 in nerve fibers during bone development and repair [1,2] .Numerous in vivo studies have suggested that CGRP is associated with bone development, metabolism and repair. In vitro studies have demonstrated that CGRP stimulates osteoblast proliferation, differentiation and maturation in both osteoblast cell lines and bone marrow mesenchyme strom...

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“…After these transcription factors are phosphorylated on serine residues, they form a complex with a common mediator, SMAD4, and the complex is translocated into the nucleus to activate the transcription of a specific gene [8,9]. Several natural or chemical compounds have been reported to induce osteoblast differentiation by induction of BMP and/or SMAD signaling, such as daidzein, osthole, and fraxetin [11,34,40]. Our study indicates that the production of BMP-2 increases in syringetin-treated MC3T3-E1 and hFOB cells.…”

Section: Discussionmentioning

confidence: 99%

Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein‐2/extracellular signal‐regulated kinase 1/2 pathway

Hsu

Liang

Hung

et al. 2009

Molecular Nutrition Food Res

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Syringetin (3,5,7,4'-tetrahydroxy-3',5'dimethoxyflavone), a flavonoid derivative, is present in grape and wine. By means of alkaline phosphatase (ALP) activity, osteocalcin, and type I collagen ELISA, we have shown that syringetin exhibits a significant induction of differentiation in MC3T3-E1 mouse calvaria osteoblasts and human fetal osteoblastic 1.19 cell line human osteoblasts. ALP and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively. Our results indicate that syringetin stimulates osteoblast differentiation at various stages, from maturation to terminally differentiated osteoblasts. Induction of differentiation by syringetin is associated with increased bone morphogenetic protein-2 (BMP-2) production. The BMP-2 antagonist noggin blocked syringetin-mediated ALP activity and osteocalcin secretion enhancement, indicating that BMP-2 production is required in syringetin-mediated osteoblast maturation and differentiation. Induction of differentiation by syringetin is associated with increased activation of SMAD1/5/8 and extracellular signal-regulated kinase 1/2 (ERK1/2). Cotreatment of ERK1/2 inhibitor 2'-amino-3'-methoxyflavone inhibited syringetin-mediated ALP upregulation and osteocalcin production. In conclusion, syringetin increased BMP-2 synthesis, and subsequently activated SMAD1/5/8 and ERK1/2, and this effect may contribute to its action on the induction of osteoblast maturation and differentiation, followed by an increase of bone mass.

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Bone Morphogenetic Protein-2 and -4 (BMP-2 and -4) Mediates Fraxetin-Induced Maturation and Differentiation in Human Osteoblast-Like Cell Lines

Cited by 25 publications

References 37 publications

8-Prenylkaempferol accelerates osteoblast maturation through bone morphogenetic protein-2/p38 pathway to activate Runx2 transcription

8-Prenylkaempferol accelerates osteoblast maturation through bone morphogenetic protein-2/p38 pathway to activate Runx2 transcription

Calcitonin gene-related peptide stimulates BMP-2 expression and the differentiation of human osteoblast-like cells in vitro

Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein‐2/extracellular signal‐regulated kinase 1/2 pathway

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