CLC number: Q813; R68
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2009-03-25
Cited: 16
Clicked: 7410
Jin-jing WANG, Feng YE, Li-jia CHENG, Yu-jun SHI, Ji BAO, Huai-qiang SUN, Wei WANG, Peng ZHANG, Hong BU. Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor[J]. Journal of Zhejiang University Science B, 2009, 10(5): 355-367.
@article{title="Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor",
author="Jin-jing WANG, Feng YE, Li-jia CHENG, Yu-jun SHI, Ji BAO, Huai-qiang SUN, Wei WANG, Peng ZHANG, Hong BU",
journal="Journal of Zhejiang University Science B",
volume="10",
number="5",
pages="355-367",
year="2009",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0820252"
}
%0 Journal Article
%T Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor
%A Jin-jing WANG
%A Feng YE
%A Li-jia CHENG
%A Yu-jun SHI
%A Ji BAO
%A Huai-qiang SUN
%A Wei WANG
%A Peng ZHANG
%A Hong BU
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 5
%P 355-367
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820252
TY - JOUR
T1 - Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor
A1 - Jin-jing WANG
A1 - Feng YE
A1 - Li-jia CHENG
A1 - Yu-jun SHI
A1 - Ji BAO
A1 - Huai-qiang SUN
A1 - Wei WANG
A1 - Peng ZHANG
A1 - Hong BU
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 5
SP - 355
EP - 367
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820252
Abstract: Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialoprotein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0- and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.
[1] Abreu, J.G., Ketpura, N.I., Reversade, B., de Robertis, E.M., 2002. Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat. Cell Biol., 4(8):599-604.
[2] Alden, T.D., Varady, P., Kallmes, D.F., Jane, J.A.Jr., Helm, G.A., 2002. Bone morphogenetic protein gene therapy. Spine, 27(16S):S87-S93.
[3] Arnott, J.A., Nuglozeh, E., Rico, M.C., Arango, H.I., Odgren, P.R., Safadi, F.F., Popoff, S.N., 2007. Connective tissue growth factor (CTGF/CCN2) is a downstream mediator for TGF-beta1-induced extracellular matrix production in osteoblasts. J. Cell. Physiol., 210(3):843-852.
[4] Betz, V.M., Betz, O.B., Harris, M.B., Vrahas, M.S., Evans, C.H., 2008. Bone tissue engineering and repair by gene therapy. Front Biosci., 13(13):833-841.
[5] Beyer Nardi, N., da Silva Meirelles, L., 2006. Mesenchymal Stem Cells: Isolation, in Vitro Expansion and Characterization. In: Stem Cells. Handbook of Experimental Pharmacology. Springer Berlin Heidelberg, Vol. 174, p.249-282.
[6] Brigstock, D.R., 2002. Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61). Angiogenesis, 5(3):153-165.
[7] Brigstock, D.R., 2003. The CCN family: a new stimulus package. J. Endocrinol., 178(2):169-175.
[8] Brigstock, D.R., Goldschmeding, R., Katsube, K.I., Lam, S.C., Lau, L.F., Lyons, K., Naus, C., Perbal, B., Riser, B., Takigawa, M., Yeger, H., 2003. Proposal for a unified CCN nomenclature. Mol. Pathol., 56(2):127-128.
[9] Caterson, E., Nesti, L., Danielson, K., Tuan, R., 2002. Human marrow-derived mesenchymal progenitor cells. Mol. Biotechnol., 20(3):245-256.
[10] Chan, J., O'Donoghue, K., de la Fuente, J., Roberts, I.A., Kumar, S., Morgan, J.E., Fisk, N.M., 2005. Human fetal mesenchymal stem cells as vehicles for gene delivery. Stem. Cells, 23(1):93-102.
[11] Cho, H.H., Park, H.T., Kim, Y.J., Bae, Y.C., Suh, K.T., Jung, J.S., 2005. Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J. Cell. Biochem., 96(3):533-542.
[12] Duan, X., Yang, L., Dong, S., Xin, R., Chen, G., Guo, L., 2008. Characterization of EGFP-labeled mesenchymal stem cells and redistribution of allogeneic cells after subcutaneous implantation. Archives of Orthopaedic and Trauma Surgery, 128(7):751-759.
[13] Edgar, C.M., Chakravarthy, V., Barnes, G., Kakar, S., Gerstenfeld, L.C., Einhorn, T.A., 2007. Autogenous regulation of a network of bone morphogenetic proteins (BMPs) mediates the osteogenic differentiation in murine marrow stromal cells. Bone, 40(5):1389-1398.
[14] Gamradt, S.C., Lieberman, J.R., 2004. Genetic modification of stem cells to enhance bone repair. Ann. Biomed. Eng., 32(1):136-147.
[15] Gersbach, C.A., Le Doux, J.M., Guldberg, R.E., Garcia, A.J., 2006. Inducible regulation of Runx2-stimulated osteogenesis. Gene Ther., 13(11):873-882.
[16] Goessler, U.R., Riedel, K., Hormann, K., Riedel, F., 2006. Perspectives of gene therapy in stem cell tissue engineering. Cells Tissues Organs, 183(4):169-179.
[17] Heng, E.C., Huang, Y., Black, S.A.Jr., Trackman, P.C., 2006. CCN2, connective tissue growth factor, stimulates collagen deposition by gingival fibroblasts via module 3 and alpha6- and beta1 integrins. J. Cell. Biochem., 98(2):409-420.
[18] Howard, D., Buttery, L.D., Shakesheff, K.M., Roberts, S.J., 2008. Tissue engineering: strategies, stem cells and scaffolds. J. Anat., 213(1):66-72.
[19] Huang, W., Rudkin, G.H., Carlsen, B., Ishida, K., Ghasri, P., Anvar, B., Yamaguchi, D.T., Miller, T.A., 2002. Overexpression of BMP-2 modulates morphology, growth, and gene expression in osteoblastic cells. Exp. Cell Res., 274(2):226-234.
[20] Igarashi, M., Kamiya, N., Hasegawa, M., Kasuya, T., Takahashi, T., Takagi, M., 2004. Inductive effects of dexamethasone on the gene expression of Cbfa1, osterix and bone matrix proteins during differentiation of cultured primary rat osteoblasts. J. Mol. Histol., 35(1): 3-10.
[21] Ivkovic, S., Yoon, B.S., Popoff, S.N., Safadi, F.F., Libuda, D.E., Stephenson, R.C., Daluiski, A., Lyons, K.M., 2003. Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development, 130(12):2779-2791.
[22] Jiang, C.Y., Gui, C., He, A.N., Hu, X.Y., Chen, J., Jiang, Y., Wang, J.A., 2008. Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction. J. Zhejiang Univ. Sci. B, 9(8):630-637.
[23] Kanaan, R.A., Aldwaik, M., Al-Hanbali, O.A., 2006. The role of connective tissue growth factor in skeletal growth and development. Med. Sci. Monit., 12(12):RA277-RA281.
[24] Kanczler, J.M., Oreffo, R.O., 2008. Osteogenesis and angiogenesis: the potential for engineering bone. Eur. Cell Mater., 15:100-114.
[25] Karp, J.M., Tanaka, T.S., Zohar, R., Sodek, J., Shoichet, M.S., Davies, J.E., Stanford, W.L., 2005. Thrombin mediated migration of osteogenic cells. Bone, 37(3):337-348.
[26] Kawaki, H., Kubota, S., Suzuki, A., Yamada, T., Matsumura, T., Mandai, T., Yao, M., Maeda, T., Lyons, K.M., Takigawa, M., 2008. Functional requirement of CCN2 for intramembranous bone formation in embryonic mice. Biochem. Biophys. Res. Commun., 366(2):450-456.
[27] Kofron, M.D., Laurencin, C.T., 2006. Bone tissue engineering by gene delivery. Adv. Drug Deliv. Rev., 58(4):555-576.
[28] Kubota, S., Takigawa, M., 2007. Role of CCN2/CTGF/Hcs24 in bone growth. Int. Rev. Cytol., 257:1-41.
[29] Lee, H.S., Huang, G.T., Chiang, H., Chiou, L.L., Chen, M.H., Hsieh, C.H., Jiang, C.C., 2003. Multipotential mesenchymal ctem cells from femoral cone carrow cear the cite of osteonecrosis. Stem. Cells, 21(2):190-199.
[30] Lee, R.H., Kim, B., Choi, I., Kim, H., Choi, H.S., Suh, K., Bae, Y.C., Jung, J.S., 2004. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol. Biochem., 14(4-6):311-324.
[31] Lin, Y., Luo, E., Chen, X., Liu, L., Qiao, J., Yan, Z., Li, Z., Tang, W., Zheng, X., Tian, W., 2005. Molecular and cellular characterization during chondrogenic differentiation of adipose tissue-derived stromal cells in vitro and cartilage formation in vivo. J. Cell. Mol. Med., 9(4):929-939.
[32] Liu, L.D., Shi, H.J., Jiang, L., Wang, L.C., Ma, S.H., Dong, C.H., Wang, J.J., Zhao, H.L., Liao, Y., Li, Q.H., 2007. The repairing effect of a recombinant human connective-tissue growth factor in a burn-wounded rhesus-monkey (Macaca mulatta) model. Biotechnol. Appl. Biochem., 47(2):105-112.
[33] Luft, F.C., 2008. CCN2, the connective tissue growth factor. J. Mol. Med., 86(1):1-3.
[34] Luo, Q., Kang, Q., Si, W., Jiang, W., Park, J.K., Peng, Y., Li, X., Luu, H.H., Luo, J., Montag, A.G., Haydon, R.C., He, T.C., 2004. Connective tissue growth factor (CTGF) is regulated by WNT and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells. J. Biol. Chem., 279(53):55958-55968.
[35] Mauney, J.R., Volloch, V., Kaplan, D.L., 2005. Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects. Tissue Eng., 11(5-6):787-802.
[36] Meijer, G.J., de Bruijn, J.D., Koole, R., van Blitterswijk, C.A., 2007. Cell-based bone tissue engineering. PLoS. Med., 4(2):e9.
[37] Mercurio, S., Latinkic, B., Itasaki, N., Krumlauf, R., Smith, J.C., 2004. Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex. Development, 131(9):2137-2147.
[38] Nishida, T., Nakanishi, T., Asano, M., Shimo, T., Takigawa, M., 2000. Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro. J. Cell. Physiol., 184(2):197-206.
[39] Nishida, T., Kawaki, H., Baxter, R.M., Deyoung, R.A., Takigawa, M., Lyons, K.M., 2007. CCN2 (connective cissue crowth cactor) is essential for extracellular matrix production and integrin signaling in chondrocytes. J. Cell Commun. Signal., 1(1):45-58.
[40] Oakes, D.A., Lieberman, J.R., 2000. Osteoinductive applications of regional gene therapy: ex vivo gene transfer. Clin. Orthop. Relat. Res., 379(Suppl.):S101-S112.
[41] Ono, M., Kubota, S., Fujisawa, T., Sonoyama, W., Kawaki, H., Akiyama, K., Oshima, M., Nishida, T., Yoshida, Y., Suzuki, K., et al., 2007. Promotion of attachment of human bone marrow stromal cells by CCN2. Biochem. Biophys. Res. Commun., 357(1):20-25.
[42] Ono, M., Kubota, S., Fujisawa, T., Sonoyama, W., Kawaki, H., Akiyama, K., Shimono, K., Oshima, M., Nishida, T., Yoshida, Y., et al., 2008. Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2. Cell Transplant., 17(1-2):231-240.
[43] Pelled, G.G., Turgeman, G., Aslan, H., Gazit, Z., Gazit, D., 2002. Mesenchymal stem cells for bone gene therapy and tissue engineering. Curr. Pharm. Des., 8(21):1917-1928.
[44] Perbal, B., Brigstock, D.R., Lau, L.F., 2003. Report on the second international workshop on the CCN family of genes. Mol. Pathol., 56(2):80-85.
[45] Pountos, I., Corscadden, D., Emery, P., Giannoudis, P.V., 2007. Mesenchymal stem cell tissue engineering: techniques for isolation, expansion and application. Injury, 38(S4):23-33.
[46] Rachfal, A.W., Brigstock, D.R., 2005. Structural and functional properties of CCN proteins. Vitam. Horm., 70:69-103.
[47] Rose, F.R., Oreffo, R.O., 2002. Bone tissue engineering: hope vs hype. Biochem. Biophys. Res. Commun., 292(1):1-7.
[48] Rydziel, S., Stadmeyer, L., Zanotti, S., Durant, D., Smerdel-Ramoya, A., Canalis, E., 2007. Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia. J. Biol. Chem., 282(27):19762-19772.
[49] Safadi, F.F., Xu, J., Smock, S.L., Kanaan, R.A., Selim, A.H., Odgren, P.R., Marks, S.C.Jr., Owen, T.A., Popoff, S.N., 2003. Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo. J. Cell. Physiol., 196(1):51-62.
[50] Slater, B.J., Kwan, M.D., Gupta, D.M., Panetta, N.J., Longaker, M.T., 2008. Mesenchymal cells for skeletal tissue engineering. Expert. Opin. Biol. Ther., 8(7):885-893.
[51] van Damme, A., van den Driessche, T., Collen, D., Chuah, M.K., 2002. Bone marrow stromal cells as targets for gene therapy. Curr. Gene Ther., 2(2):195-209.
[52] Xiang, Y., Zheng, Q., Jia, B.B., Huang, G.P., Xu, Y.L., Wang, J.F., Pan, Z.J., 2007. Ex vivo expansion and pluripotential differentiation of cryopreserved human bone marrow mesenchymal stem cells. J. Zhejiang Univ. Sci. B, 8(2): 136-146.
[53] Yamaai, T., Nakanishi, T., Asano, M., Nawachi, K., Yoshimichi, G., Ohyama, K., Komori, T., Sugimoto, T., Takigawa, M., 2005. Gene expression of connective tissue growth factor (CTGF/CCN2) in calcifying tissues of normal and cbfa1-null mutant mice in late stage of embryonic development. J. Bone Miner. Metab., 23(4): 280-288.
[54] Yamanaka, O., Saika, S., Ikeda, K., Miyazaki, K., Kitano, A., Ohnishi, Y., 2008. Connective tissue growth factor modulates extracellular matrix production in human subconjunctival fibroblasts and their proliferation and migration in vitro. Jpn. J. Ophthalmol, 52(1):8-15.
Open peer comments: Debate/Discuss/Question/Opinion
<1>