Skip to main content
Erschienen in: Journal of Bone and Mineral Metabolism 6/2014

01.11.2014 | Original Article

Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts

verfasst von: Peipei Li, Yan Bai, Guangfu Yin, Ximing Pu, Zhongbing Huang, Xiaoming Liao, Xianchun Chen, Yadong Yao

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

In the present study, the effects of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were investigated. It was found that the proliferation, differentiation and mineralization of ROBs were all dose-dependently increased at particular times in the case of treatment with only one growth factor. To investigate the effects of combined treatment, ROBs were treated with either a single application of a relatively high dose of each growth factor, or binary/triple combined applications of relatively low doses of the growth factors. Osteogenic differentiation was significantly promoted in the triple combination treatment of BMP-2, VEGF and bFGF compared with the single or binary combination treatments. The optimal timing of the triple combination to enhance osteogenesis was also tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were added in the late stage, osteogenic differentiation of ROBs could be enhanced more effectively. These results could be used to construct bone tissue engineering scaffolds that release growth factors sequentially.
Literatur
1.
Zurück zum Zitat Zhao Z, Zhao M, Xiao G, Franceschi RT (2005) Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo. Mol Ther 12:247–253PubMedCrossRef Zhao Z, Zhao M, Xiao G, Franceschi RT (2005) Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo. Mol Ther 12:247–253PubMedCrossRef
2.
Zurück zum Zitat Fu Y-C, Nie H, Ho M-L, Wang C-K, Wang C-H (2008) Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnol Bioeng 99:996–1006PubMedCrossRef Fu Y-C, Nie H, Ho M-L, Wang C-K, Wang C-H (2008) Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnol Bioeng 99:996–1006PubMedCrossRef
3.
Zurück zum Zitat Nie H, Soh BW, Fu Y-C, Wang C-H (2008) Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery. Biotechnol Bioeng 99:223–234PubMedCrossRef Nie H, Soh BW, Fu Y-C, Wang C-H (2008) Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery. Biotechnol Bioeng 99:223–234PubMedCrossRef
4.
Zurück zum Zitat Kempen DHR, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, Yaszemski MJ, Dhert WJA (2009) Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 30:2816–2825PubMedCrossRef Kempen DHR, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, Yaszemski MJ, Dhert WJA (2009) Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 30:2816–2825PubMedCrossRef
5.
Zurück zum Zitat Deckers MM, Karperien M, van der Bent C, Yamashita T, Papapoulos SE, Löwik CW (2000) Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology 141:1667–1674PubMedCrossRef Deckers MM, Karperien M, van der Bent C, Yamashita T, Papapoulos SE, Löwik CW (2000) Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology 141:1667–1674PubMedCrossRef
6.
Zurück zum Zitat Grasselli F, Basini G, Bussolati S, Tamanini C (2002) Effects of VEGF and bFGF on proliferation and production of steroids and nitric oxide in porcine granulosa cells. Reprod Domest Anim 37:362–368PubMedCrossRef Grasselli F, Basini G, Bussolati S, Tamanini C (2002) Effects of VEGF and bFGF on proliferation and production of steroids and nitric oxide in porcine granulosa cells. Reprod Domest Anim 37:362–368PubMedCrossRef
7.
Zurück zum Zitat Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, Takagishi K, Kato Y (2001) Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 288:413–419PubMedCrossRef Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, Takagishi K, Kato Y (2001) Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 288:413–419PubMedCrossRef
8.
Zurück zum Zitat Fujimura K, Bessho K, Okubo Y, Kusumoto K, Segami N, Lizuka T (2002) The effect of fibroblast growth factor-2 on the osteoinductive activity of recombinant human bone morphogenetic protein-2 in rat muscle. Arch Oral Biol 47:577–584PubMedCrossRef Fujimura K, Bessho K, Okubo Y, Kusumoto K, Segami N, Lizuka T (2002) The effect of fibroblast growth factor-2 on the osteoinductive activity of recombinant human bone morphogenetic protein-2 in rat muscle. Arch Oral Biol 47:577–584PubMedCrossRef
9.
Zurück zum Zitat Chaudhary LR, Hofmeister AM, Hruska KA (2004) Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone 34:402–411PubMedCrossRef Chaudhary LR, Hofmeister AM, Hruska KA (2004) Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone 34:402–411PubMedCrossRef
10.
Zurück zum Zitat Nishimori S, Tanaka Y, Chiba T, Fujii M, Imamura T, Miyazono K, Ogasawara T, Kawaguchi H, Igarashi T, Fujita T, Tanaka K, Toyoshima H (2001) Smad-mediated transcription is required for transforming growth factor-β1-induced p57Kip2 proteolysis in osteoblastic cells. J Biol Chem 276:10700–10705PubMedCrossRef Nishimori S, Tanaka Y, Chiba T, Fujii M, Imamura T, Miyazono K, Ogasawara T, Kawaguchi H, Igarashi T, Fujita T, Tanaka K, Toyoshima H (2001) Smad-mediated transcription is required for transforming growth factor-β1-induced p57Kip2 proteolysis in osteoblastic cells. J Biol Chem 276:10700–10705PubMedCrossRef
11.
Zurück zum Zitat Song I, Kim B-S, Kim C-S, Im G-I (2011) Effects of BMP-2 and vitamin D3 on the osteogenic differentiation of adipose stem cells. Biochem Biophys Res Co 408:126–131CrossRef Song I, Kim B-S, Kim C-S, Im G-I (2011) Effects of BMP-2 and vitamin D3 on the osteogenic differentiation of adipose stem cells. Biochem Biophys Res Co 408:126–131CrossRef
12.
Zurück zum Zitat Camozzi V, Tossi A, Simoni E, Pagani F, Francucci CM, Moro L (2007) Role of biochemical markers of bone remodeling in clinical practice. J Endocrinol Invest 30:13–17PubMedCrossRef Camozzi V, Tossi A, Simoni E, Pagani F, Francucci CM, Moro L (2007) Role of biochemical markers of bone remodeling in clinical practice. J Endocrinol Invest 30:13–17PubMedCrossRef
13.
Zurück zum Zitat Blanco Calvo M, Bolós Fernández V, Medina Villaamil V, Aparicio Gallego G, Díaz Prado S, Grande Pulido E (2009) Biology of BMP signaling and cancer. Clin Transl Oncol 11:126–137PubMedCrossRef Blanco Calvo M, Bolós Fernández V, Medina Villaamil V, Aparicio Gallego G, Díaz Prado S, Grande Pulido E (2009) Biology of BMP signaling and cancer. Clin Transl Oncol 11:126–137PubMedCrossRef
14.
Zurück zum Zitat Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263PubMedCrossRef Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263PubMedCrossRef
15.
Zurück zum Zitat Ryoo HM, Lee MH, Kim YJ (2006) Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366:51–57PubMedCrossRef Ryoo HM, Lee MH, Kim YJ (2006) Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366:51–57PubMedCrossRef
16.
Zurück zum Zitat Peng H, Usas A, Olshanski A, Ho AM, Gearhart B, Cooper GM, Huard J (2005) VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis. J Bone Miner Res 20:2017–2027PubMedCrossRef Peng H, Usas A, Olshanski A, Ho AM, Gearhart B, Cooper GM, Huard J (2005) VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis. J Bone Miner Res 20:2017–2027PubMedCrossRef
17.
Zurück zum Zitat Celil AB, Campbell PG (2005) BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 280:31353–31359PubMedCrossRef Celil AB, Campbell PG (2005) BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 280:31353–31359PubMedCrossRef
18.
Zurück zum Zitat Deschaseaux F, Sensébée L, Heymann D (2009) Mechanisms of bone repair and regeneration. Trends Mol Med 15:417–429PubMedCrossRef Deschaseaux F, Sensébée L, Heymann D (2009) Mechanisms of bone repair and regeneration. Trends Mol Med 15:417–429PubMedCrossRef
19.
Zurück zum Zitat Maegawa N, Kawamura K, Hirose M, Yajima H, Takakura Y, Ohgushi H (2007) Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2). J Tissue Eng Regen Med 1:306–313PubMedCrossRef Maegawa N, Kawamura K, Hirose M, Yajima H, Takakura Y, Ohgushi H (2007) Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2). J Tissue Eng Regen Med 1:306–313PubMedCrossRef
20.
Zurück zum Zitat Fakhry A, Ratisoontorn C, Vedhachalam C, Salhab I, Koyama E, Leboy P, Pacifici M, Kirschner RE, Nah H-D (2005) Effects of FGF-2/-9 in calvarial bone cell cultures: differentiation stage-dependent mitogenic effect, inverse regulation of BMP-2 and noggin, and enhancement of osteogenic potential. Bone 36:254–266PubMedCrossRef Fakhry A, Ratisoontorn C, Vedhachalam C, Salhab I, Koyama E, Leboy P, Pacifici M, Kirschner RE, Nah H-D (2005) Effects of FGF-2/-9 in calvarial bone cell cultures: differentiation stage-dependent mitogenic effect, inverse regulation of BMP-2 and noggin, and enhancement of osteogenic potential. Bone 36:254–266PubMedCrossRef
Metadaten
Titel
Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts
verfasst von
Peipei Li
Yan Bai
Guangfu Yin
Ximing Pu
Zhongbing Huang
Xiaoming Liao
Xianchun Chen
Yadong Yao
Publikationsdatum
01.11.2014
Verlag
Springer Japan
Erschienen in
Journal of Bone and Mineral Metabolism / Ausgabe 6/2014
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-013-0538-6

Weitere Artikel der Ausgabe 6/2014

Journal of Bone and Mineral Metabolism 6/2014 Zur Ausgabe

List of Reviewers 2013-2014

List of reviewers 2013–2014

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.