Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow‑derived mesenchymal stem cells

Lin,Zhaowei; Wang,Jiang‑Sheng; Lin,Lijun; Zhang,Jingwen; Liu,Yunlong; Shuai,Ming; Li,Qi

doi:10.3892/etm.2013.1464

2014-March Volume 7 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

2014-March Volume 7 Issue 3

Full Size Image

Article

Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow‑derived mesenchymal stem cells

Authors:
- Zhaowei Lin
- Jiang‑Sheng Wang
- Lijun Lin
- Jingwen Zhang
- Yunlong Liu
- Ming Shuai
- Qi Li
View Affiliations / Copyright

Affiliations: Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Orthopaedics, Lund University Hospital, S‑22185 Lund, Sweden, Department of Orthopaedic Rehabilitation, Guangdong Provincial Work Injury Rehabilitation Center, Guangzhou, Guangdong 510440, P.R. China
Pages: 625-629
|
Published online on: December 27, 2013

https://doi.org/10.3892/etm.2013.1464
Expand metrics +

Abstract

Bone marrow‑derived mesenchymal stem cells (MSCs) are dominant seed cell sources for bone regeneration. Bone morphogenetic proteins (BMPs) initiate cartilage and bone formation in a sequential cascade. Vascular endothelial growth factor (VEGF) is an essential coordinator of extracellular matrix remodeling, angiogenesis and bone formation. In the present study, the effects of the vascular endothelial growth factor 165 (VEGF165) and bone morphogenetic protein 2 (BMP2) genes on bone regeneration were investigated by the lentivirus‑mediated cotransfection of the two genes into rat bone marrow‑derived MSCs. The successful co‑expression of the two genes in the MSCs was confirmed using quantitative polymerase chain reaction (qPCR) and western blot analysis. The results of alizarin red and alkaline phosphatase (ALP) staining at 14 days subsequent to transfection showed that the area of staining in cells transfected with BMP2 alone was higher than that in cells transfected with BMP2 and VEGF165 or untransfected control cells, while the BMP2 + VEGF165 group showed significantly more staining than the untransfected control. This indicated that BMP2 alone exhibited a stronger effect in bone regeneration than BMP2 in combination with VEGF165. Similarly, in inducing culture medium, the ALP activity of the BMP2 + VEGF165 group was notably suppressed compared with that of the BMP2 group. The overexpression of VEGF165 inhibited BMP2‑induced MSC differentiation and osteogenesis in vitro. Whether or not local VEGF gene therapy is likely to affect bone regeneration in vivo requires further investigation.

View Figures

View References

1	Wang Y, Zeng B and Li X: Expression of human calcitonin by microencapsulated recombinant myoblasts. Biotechnol Lett. 28:1453–1458. 2006. View Article : Google Scholar : PubMed/NCBI
2	Roldán JC, Detsch R, Schaefer S, et al: Bone formation and degradation of a highly porous biphasic calcium phosphate ceramic in presence of BMP-7, VEGF and mesenchymal stem cells in an ectopic mouse model. J Craniomaxillofac Surg. 38:423–430. 2010.PubMed/NCBI
3	Peng H, Wright V, Usas A, et al: Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest. 110:751–759. 2002. View Article : Google Scholar : PubMed/NCBI
4	Kiyozuka Y, Miyazaki H, Yoshizawa K, et al: An autopsy case of malignant mesothelioma with osseous and cartilaginous differentiation: bone morphogenetic protein-2 in mesothelial cells and its tumor. Dig Dis Sci. 44:1626–1631. 1999. View Article : Google Scholar : PubMed/NCBI
5	Zelzer E, McLean W, Ng YS, et al: Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development. 129:1893–1904. 2002.PubMed/NCBI
6	Deckers MM, van Bezooijen RL, van der Horst G, et al: Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A. Endocrinology. 143:1545–1553. 2002. View Article : Google Scholar : PubMed/NCBI
7	Tsuda H, Wada T, Yamashita T and Hamada H: Enhanced osteoinduction by mesenchymal stem cells transfected with a fiber-mutant adenoviral BMP2 gene. J Gene Med. 7:1322–1334. 2005. View Article : Google Scholar : PubMed/NCBI
8	Reddi AH: Bone and cartilage differentiation. Curr Opin Genet Dev. 32:737–744. 1994. View Article : Google Scholar
9	Ishihara A and Bertone A: Cell-mediated and direct gene therapy for bone regeneration. Expert Opin Biol Ther. 12:411–423. 2012. View Article : Google Scholar : PubMed/NCBI
10	Lieberman JR, Daluiski A, Stevenson S, et al: The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am. 81:905–917. 1999.PubMed/NCBI
11	Xiao C, Zhou H, Liu G, et al: Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration. Biomed Mater. 6:0150132011. View Article : Google Scholar : PubMed/NCBI
12	Bostrom MP, Saleh KJ and Einhorn TA: Osteoinductive growth factors in preclinical fracture and long bone defects models. Orthop Clin North Am. 30:647–658. 1999. View Article : Google Scholar : PubMed/NCBI
13	Kujala S, Raatikainen T, Ryhänen J, et al: Composite implant of native bovine bone morphogenetic protein (BMP) and biocoral in the treatment of scaphoid nonunions - a preliminary study. Scand J Surg. 91:186–190. 2002.PubMed/NCBI
14	Furumatsu T, Shen ZN, Kawai A, et al: Vascular endothelial growth factor principally acts as the main angiogenic factor in the early stage of human osteoblastogenesis. J Biochem. 33:633–639. 2003. View Article : Google Scholar
15	Murphy WL, Peters MC, Kohn DH and Mooney DJ: Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering. Biomaterials. 21:2521–2527. 2000. View Article : Google Scholar : PubMed/NCBI
16	Goad DL, Rubin J, Wang H, et al: Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I. Endocrinology. 137:2262–2268. 1996.PubMed/NCBI
17	Kempen DH, Lu L, Heijink A, et al: Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials. 30:2816–2825. 2009. View Article : Google Scholar : PubMed/NCBI
18	Wu GP, He XC, Yang ZH and Guo L: Influence on the osteogenic activity of the human bone marrow mesenchymal stem cells transfected by liposome-mediated recombinant plasmid pIRES-hBMP2-hVEGF165 in vitro. Ann Plast Surg. 65:80–84. 2010. View Article : Google Scholar
19	Schönmeyr BH, Soares M, Avraham T, et al: Vascular endothelial growth factor inhibits bone morphogenetic protein 2 expression in rat mesenchymal stem cells. Tissue Eng Part A. 16:653–662. 2010.PubMed/NCBI
20	Kuroda S, Sumner DR and Virdi AS: Effects of TGF-β1 and VEGF-A transgenes on the osteogenic potential of bone marrow stromal cells in vitro and in vivo. J Tissue Eng. 3:20417314124597452012.
21	Song XB, Liu SH, Qu X, et al: BMP2 and VEGF promote angiogenesis but retard terminal differentiation of osteoblasts in bone regeneration by up-regulating Id1. Acta Biochim Biophys Sin (Shanghai). 43:796–804. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow‑derived mesenchymal stem cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles