Effect of insulin-like growth factor-1 on chondrogenic differentiation of bone marrow mesenchymal stem cells and expression of matrix metalloproteinase

doi:10.3969/j.issn.2095-4344.2013.19.001

Abstract

Abstract:

BACKGROUND: Studies have shown that insulin-like growth factor-1 serves as a helper factor and is combined combines with other factors to promote the differentiation of bone marrow mesenchymal stem
cells into chondrocytes. However, whether insulin-like growth factor-1 alone could promote the secretion of cartilage specific collagen remains controversial, and its effect on cell proliferation and stability of cartilage collagenfiber has been rarely reported.
OBJECTIVE: To investigate the effect of insulin-like growth factor-1 on chondrogenic differentiation and matrix metalloproteinase expression of bone marrow mesenchymal stem cells.
METHODS: The expression vector carrying complete coding sequence of insulin-like growth factor-1 was constructed, and stably transfected to rat bone marrow mesenchymal stem cells, serving as insulin-like growth factor-1 stable transfection group. Meanwhile, the non-transfection group was taken as the control.
RESULTS AND CONCLUSION: The 3-(4,5)-dimethylthiahiazo-2-yl-3,5-di-phenytetrazoliumromide assay showed that, insulin-like growth factor-1 stable expressing bone marrow mesenchymal stem cells was successfully established, and cell proliferation was significantly increased after 4 days of transfection (P < 0.05). Reverse transcription-polymerase chain reaction, western blot analysis and immunocytochemistry detection showed that, the mRNA and protein levels of insulin-like growth factor-1 and collagen type Ⅱ were significantly increased in the stable transfection group (P < 0.01), while mRNA levels of matrix metalloproteinase-1, -2 and -3 were significantly decreased compared with the non-transfection group (P < 0.01). Experimental findings confirm that, insulin-like growth factor-1 alone can promote the proliferation of bone marrow mesenchymal stem cells as well as chondrogenic differentiation, and maintain the stability of collagen fibers.

Key words: stem cells, bone marrow-derived stem cells, insulin-like growth factor-1, bone marrow mesenchymal stem cells, vector construction, cell proliferation, chondrogenic differentiation, collagen type Ⅱ, matrix metalloproteinase, tissue-engineered cartilage, other grants-supported paper, stem cell photographs-containing paper

CLC Number:

R394.2

Wu Bo, Ma Xu, Zhu Da-mu, Liu Su-yuan, Wang Jing-xu, Zhang Yi, Fu Ai-min, Pan Liang. Effect of insulin-like growth factor-1 on chondrogenic differentiation of bone marrow mesenchymal stem cells and expression of matrix metalloproteinase[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(19): 3421-3429.

Figures/Tables 4

References

[1] Yu J, Yan YH, Wan T. Shengwu GukeCailiao yu Linchuang Yanjiu. 2005;2(3):31-36.于娟,闫玉华,万涛.软骨组织工程研究进展[J].生物骨科材料与临床研究,2005,2(3):31-36.

[2] Chajra H, Rousseau CF, Cortial D, et al. Collagen-based biomaterials and cartilage engineering. Application to osteochondral defects. Biomed Mater Eng. 2008;18(Suppl 1): S33-45.

[3] Jadlowiec JA, Celil AB, Hollinger JO. Bone tissue engineering: recent advances and promising therapeutic agents. Expert Opin Biol Ther. 2003;3(3):409-423.

[4] Cui L, Zhang Y, Li XL, et al. Guoji Shengwu Yixue Gongcheng Zazhi. 2010;33(6):367-371.崔丽,张扬,李秀兰,等.骨髓间充质干细胞用于软骨组织工程的研究进展[J].国际生物医学工程杂志,2010,33(6):367-371.

[5] Yoon DM, Fisher JP. Effects of exogenous IGF-1 delivery on the early expression of IGF-1 signaling molecules by alginate embedded chondrocytes. Tissue Eng Part A. 2008;14(7): 1263-1273.

[6] Legendre F, Ollitrault D, Hervieu M, et al. Enhanced hyaline cartilage matrix synthesis in collagen sponge scaffolds by using si RNA to stabilize chondrocytes phenotype culture with BMP-2 under gypoxia. Tissue Eng Part C Methods. 2013.

[7] Rodrigues MT, Lee SJ, Gomes ME, et al. Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells. Acta Biomater. 2012;8(7):2795-2806.

[8] Yan J, Liu LR, Zhang QQ. Zhongguo Xiufu Chongjian Waike Zazhi. 2006;20(11):1114-1118.晏杰,刘玲蓉,张其清.诱导骨髓间充质干细胞向软骨细胞分化的体外研究[J].中国修复重建外科杂志,2006,20(11): 1114-1118.

[9] Fu Q, Gong SY, Yang LQ, et al. Zhongguo Xiandai Yixue Zazhi. 2008;18(6):694-698.付勤,宫树一,杨礼庆,等.脂质体介导胰岛素样生长因子1基因修饰骨髓间充质干细胞成软骨分化[J].中国现代医学杂志,2008, 18(6):694-698.

[10] Ma WM, Dong QR, Xie ZG, et al. Zhongguo Xiandai Yixue Zazhi. 2011;(3):5-7.马文明,董启榕,谢宗刚,等.MMP-1、MMP-13在大树骨关节炎软骨中的表达[J].中国现代医药杂志,2011,3:5-7.

[11] Zhang M, Zhou Q, Liang QQ, et al. IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways. Osteoarthritis Cartilage. 2009;17(1):100-106.

[12] Wang N, Yang SY, Chu JX. Xiandai Shenjing Jibing Zazhi. 2003; 3(3):174-177.王宁,杨树源,褚建新.骨髓间充质干细胞的生物学特征及其应用[J].现代神经疾病杂志,2003,3(3):174-177.

[13] Barry FP, Murphy JM. Mesenchymal stem cells:clinical applications and biological characterization. Int J Biochem Cell Biol. 2004;36(4):568-584.

[14] Deng J, Petersen BE, Steindler DA, et al. Mesenchymal stem cells spontaneously express neral proteins in culture and are neurogenic after transplantation. Stem Cells. 2006;24(4): 1054-1064.

[15] Schmidt MB, Chen EH, Lynch SE. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthritis Cartilage. 2006;14(5):403-412.

[16] Beriat GK, Akmansu SH, Dogan C, et al. The effect of subcutaneous insulin-like groth factor-1(IGF-1) injuction on rabbit auricular cartilage autograft viability. Bosh J Basic Med Sci. 2012;12(4):213-218.

[17] Nadzir MM, Kino-Oka M, Suqawara K, et al. Modulation of chondrocyte migration and aggregation by insulin-like growth factor-1 in cultured cartilage. Biotechnol Lett. 2013;35(2): 295-300.

[18] Zhao G, Fu Q, Shen T. Zhongguo Yike Daxue Xuebao. 2008; 37(4):513-514.赵广,付勤,沈涛.IGF-1对成兔关节软骨细胞体外增殖的影响[J].中国医科大学学报,2008,37(4):513-514.

[19] Zhang CH, Yang J, Li JJ, et al. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang kangfu. 2010;14(28):5131-5135.张传辉,杨军,李建军,等.兔脂肪干细胞体外构建组织工程软骨:负载胰岛素样生长因子1基因的作用[J].中国组织工程研究与临床康复,2010,14(28):5131-5135.

[20] Bonassar LJ, Grodzinsky AJ, Frank EH, et al. The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-1. J Orthop Res. 2001;19(1):11-17.

[21] Li TX, Jiao YT, Wang DZ, et al. Huaxi Kouqiang Yixue Zazhi. 2000;(01):12-15.李唐新,焦岩涛,王大章,等.生长因子对人髁突软骨细胞I、II、IⅡ型前胶原基因表达的调控研究[J].华西口腔医学杂志,2000,(1): 12-15.

[22] Zhou Q, Deng ZS, Zhu Y, et al. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang kangfu. 2010;14(10):1785-1790.周全,邓展生,朱勇,等.胰岛素样生长因子1对人脂肪来源的间充质干细胞向软骨细胞定向诱导分化的作用[J].中国组织工程研究与临床康复,2010,14(10):1785-1790.

[23] Longobardi L, O’Rear L, Aakula S, et al. Effect of IGF-1 in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J Bone Miner Res. 2006;21(4):626-636.

[24] Lo MY, Kim HT. Chondrocyte apoptosis induced by collagen degradation: inhibition by caspase inhibitors and IGF-1. J Orthop Res. 2004;22(1):140-144.

[25] Nixon AJ, Brower-Toland BD, Bent SJ, et al. Insulinlike growth factor-1 gene therapy applications for cartilage repair. Clin Orthop Relat Res. 2000;379(Suppl):S201-213.

[26] Wang YB, Chen AM, Guo JF. Zhongguo Jiaoxing Waike Zazhi. 2007;15(11):853-855.王玉彬,陈安民,郭风劲,等.基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究[J].中国矫形外科杂志,2007,15(11):853-855.

[27] Jakobs M, Haupl T, Krenn V, et al. MMP-and FAP-mediated non-inflammation-related destruction of cartilage and bone in rheumatoid arthritis. Z Rheumatol. 2009;68(8):683-694.

[28] Wu HB, Du JY, Hu Y, et al. Zhonghua Fengshibingxue Zazhi. 2002;6(3):169-173.吴宏斌,杜靖远,胡勇,等.兔前交叉韧带切断骨关节炎模型中MMP-1、MMP-13及TIMP-1 mRNA表达研究[J].中华风湿病学杂志,2002,6(3):169-173.

[29] Lu JP, Shu J, Xiong Y, et al. Guoji Gukexue Zazhi. 2007;28(4): 273-276.陆继鹏,舒钧,熊鹰,等.软骨下骨刚度增加对关节软骨Ⅱ型胶原和MMP-1表达的影响[J].国际骨科学杂志,2007,28(4):273-276.

[30] Zhang M, Zhou Q, Liang QQ, et al. IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways. Osteoarthritis Cartilage. 2009;17(1):100-106.

[31] Montaseri A, Busch F, Mobasheri A, et al. IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-kB signaling: involvement of Src/PI-3K/AKT pathway. PLoS One. 2011;6(12):e28663.

[32] The Ministry of Science and Technology of the People’s Republic of China. Guidance Suggestions for the Care and Use of Laboratory Animals. 2006-09-30.