Effect of fibroblast growth factor 9 on the osteogenic differentiation of bone marrow stromal stem cells and dental pulp stem cells

Lu,Jingting; Dai,Jiewen; Wang,Xudong; Zhang,Maolin; Zhang,Peng; Sun,Hao; Zhang,Xiuli; Yu,Hongbo; Zhang,Wenbin; Zhang,Lei; Jiang,Xinquan; Shen,Steve  Guofang

doi:10.3892/mmr.2014.2998

Effect of fibroblast growth factor 9 on the osteogenic differentiation of bone marrow stromal stem cells and dental pulp stem cells

Authors:
- Jingting Lu
- Jiewen Dai
- Xudong Wang
- Maolin Zhang
- Peng Zhang
- Hao Sun
- Xiuli Zhang
- Hongbo Yu
- Wenbin Zhang
- Lei Zhang
- Xinquan Jiang
- Steve Guofang Shen
View Affiliations

Affiliations: Department of Oral and Craniomaxillofacial Science, Shanghai Ninth People's Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China, Oral Bioengineering Lab, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
Published online on: November 26, 2014 https://doi.org/10.3892/mmr.2014.2998
Pages: 1661-1668
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The role of fibroblast growth factor 9 (FGF9) in bone formation may depend on gene dosage, developmental stage, cell type or interactions with other cytokines. In the present study bone marrow stromal stem cells (BMSCs) and dental pulp stem cells (DPSCs) were cultured and osteogenically induced in vitro, treated with exogenous FGF9 at varying concentrations. Alkaline phosphatase staining, alizarin red S staining, reverse transcription quantitative polymerase chain reaction and western blot analyses were performed in order to investigate the gene expression levels of osteogenic markers. The results of the present study demonstrated that FGF9 enhanced the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2) during osteogenic induction in BMSCs and DPSCs, which are derived from different tissues. FGF9 also inhibited the osteogenic differentiation of BMSCs and DPSCs through the activation of ERK1/2. These findings suggested that FGF9 may be an inhibitor of osteogenesis in mesenchymal stem cells in vitro and its application in vivo requires investigation in the future.

View Figures

View References

1	Sylvestersen KB, Herrera PL, Serup P and Rescan C: Fgf9 signalling stimulates Spred and Sprouty expression in embryonic mouse pancreas mesenchyme. Gene Expr Patterns. 11:105–111. 2011. View Article : Google Scholar
2	Geske MJ, Zhang X, Patel KK, Ornitz DM and Stappenbeck TS: Fgf9 signaling regulates small intestinal elongation and mesenchymal development. Development. 135:2959–2968. 2008. View Article : Google Scholar : PubMed/NCBI
3	White AC, Lavine KJ and Ornitz DM: FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network. Development. 134:3743–3752. 2007. View Article : Google Scholar : PubMed/NCBI
4	Hung IH, Yu K, Lavine KJ and Ornitz DM: FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod. Dev Biol. 307:300–313. 2007. View Article : Google Scholar : PubMed/NCBI
5	Govindarajan V and Overbeek PA: FGF9 can induce endochondral ossification in cranial mesenchyme. BMC Dev Biol. 6:72006. View Article : Google Scholar : PubMed/NCBI
6	DiNapoli L, Batchvarov J and Capel B: FGF9 promotes survival of germ cells in the fetal testis. Development. 133:1519–1527. 2006. View Article : Google Scholar : PubMed/NCBI
7	Behr B, Leucht P, Longaker MT and Quarto N: Fgf-9 is required for angiogenesis and osteogenesis in long bone repair. Proc Natl Acad Sci USA. 107:11853–11858. 2010. View Article : Google Scholar : PubMed/NCBI
8	Ignelzi MA Jr, Wang W and Young AT: Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. J Bone Miner Res. 18:751–759. 2003. View Article : Google Scholar : PubMed/NCBI
9	Fakhry A, Ratisoontorn C, Vedhachalam C, et al: 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. 36:254–266. 2005. View Article : Google Scholar : PubMed/NCBI
10	Weksler NB, Lunstrum GP, Reid ES and Horton WA: Differential effects of fibroblast growth factor (FGF) 9 and FGF2 on proliferation, differentiation and terminal differentiation of chondrocytic cells in vitro. Biochem J. 342:677–682. 1999. View Article : Google Scholar : PubMed/NCBI
11	Garofalo S, Kliger-Spatz M, Cooke JL, et al: Skeletal dysplasia and defective chondrocyte differentiation by targeted overexpression of fibroblast growth factor 9 in transgenic mice. J Bone Miner Res. 14:1909–1915. 1999. View Article : Google Scholar : PubMed/NCBI
12	Wu XL, Gu MM, Huang L, et al: Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene. Am J Hum Genet. 85:53–63. 2009. View Article : Google Scholar : PubMed/NCBI
13	Dai J, Wang J, Lu J, et al: The effect of co-culturing costal chondrocytes and dental pulp stem cells combined with exogenous FGF9 protein on chondrogenesis and ossification in engineered cartilage. Biomaterials. 33:7699–7711. 2012. View Article : Google Scholar : PubMed/NCBI
14	Ornitz DM and Marie PJ: FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 16:1446–1465. 2002. View Article : Google Scholar : PubMed/NCBI
15	Zou D, Zhang Z, He J, et al: Repairing critical-sized calvarial defects with BMSCs modified by a constitutively active form of hypoxia-inducible factor-1alpha and a phosphate cement scaffold. Biomaterials. 32:9707–9718. 2011. View Article : Google Scholar : PubMed/NCBI
16	Frontini MJ, Nong Z, Gros R, et al: Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells. Nat Biotechnol. 29:421–427. 2011. View Article : Google Scholar : PubMed/NCBI
17	Komada Y, Yamane T, Kadota D, et al: Origins and properties of dental, thymic, and bone marrow mesenchymal cells and their stem cells. PLoS One. 7:e464362012. View Article : Google Scholar : PubMed/NCBI
18	Stanton LA, Underhill TM and Beier F: MAP kinases in chondrocyte differentiation. Dev Biol. 263:165–175. 2003. View Article : Google Scholar : PubMed/NCBI
19	Prasadam I, van Gennip S, Friis T, Shi W, Crawford R and Xiao Y: ERK-1/2 and p38 in the regulation of hypertrophic changes of normal articular cartilage chondrocytes induced by osteoarthritic subchondral osteoblasts. Arthritis Rheum. 62:1349–1360. 2010. View Article : Google Scholar : PubMed/NCBI
20	Zhao Y, Song T, Wang W, et al: P38 and ERK1/2 MAPKs act in opposition to regulate BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. PLoS One. 7:e433832012. View Article : Google Scholar : PubMed/NCBI
21	Twigg SR, Vorgia E, McGowan SJ, et al: Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis. Nat Genet. 45:308–313. 2013. View Article : Google Scholar : PubMed/NCBI
22	Nakamura T, Gulick J, Pratt R and Robbins J: Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations. Proc Natl Acad Sci USA. 106:15436–15441. 2009. View Article : Google Scholar : PubMed/NCBI