Uric acid effect on Wnt signaling pathways during osteogenic differentiation of human bone marrow mesenchymal stem cells

doi:10.3969/j.issn.2095-4344.2015.28.009

Abstract

Abstract:

BACKGROUND: Uric acid, as an endogenous antioxidant, exhibits anti-oxidative and anti-DNA damage effects, promotes osteogenic differentiation, and therefore has been paid more attentions.

OBJECTIVE: To investigate the effects of different concentrations of uric acid on the expression of genes related to Wnt/β-catenin signaling pathways during osteogenic differentiation of human bone marrow mesenchymal stem cells.

METHODS: Healthy adult human bone marrow mesenchymal stem cells were in vitro isolatedby adherent culture of whole bone marrow. Passage 3 bone marrow mesenchymal stem cells were induced to differentiate into osteoblasts using different concentrations of uric acid (0, 140, 280, 560 μmol/L). Alkaline phosphatase activity, cell proliferation capacity, and Wnt-3α and β-catenin mRNA expression in the Wnt signaling pathways were detected.

RESULTS AND CONCLUSION: Alkaline phosphatase staining was positive. After treatment with uric acid, alkaline phosphatase activity and cell proliferation capacity were increased, the expression of Wnt signaling pathway-related genes Wnt-3a and β-catenin was up-regulated in a dose-dependent manner. There were significant differences in the abovementioned indices between experimental groups and between each experimental group and control group (P < 0.05). These findings suggest that uric acid up-regulates Wnt-3a/β-catenin signaling pathway and thereby promotes the osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cells in a dose-dependent manner.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

CLC Number:

R394.2

Wang Xiao-li, Xu Li-li, Yang Nai-long. Uric acid effect on Wnt signaling pathways during osteogenic differentiation of human bone marrow mesenchymal stem cells[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(28): 4472-4477.

Figures/Tables 1

References

[1] Sohni A, Verfaillie CM. Mesenchymal stem cells migration homing and tracking. Stem Cells Int. 2013;2013:130763.

[2] Kim EJ, Kim N, Cho SG. The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation. Exp Mol Med. 2013;45:e2.

[3] Sharma RR, Pollock K, Hubel A, et al. Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion. 2014;54(5):1418-1437.

[4] Beane OS, Darling EM. Isolation, characterization, and differentiation of stem cells for cartilage regeneration. Ann Biomed Eng. 2012;40(10):2079-2097.

[5] Matsumoto T, Kuroda R, Mifune Y, et al. Circulating endothelial/skeletal progenitor cells for bone regeneration and healing. Bone. 2008;43(3):434-439.

[6] 彭俊琼,袁伟杰.肾脏尿酸转运体对调节尿酸的影响及尿酸在氧化应激中的双重作用[J].中华肾脏病杂志,2011,27(11):862-864.

[7] Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981;78(11):6858-6862.

[8] Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004; 20:781-810.

[9] Macsai CE, Foster BK, Xian CJ. Roles of Wnt signalling in bone growth, remodelling, skeletal disorders and fracture repair. J Cell Physiol. 2008;215(3):578-587.

[10] Liu G, Vijayakumar S, Grumolato L, et al. Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells. J Cell Biol. 2009;185(1):67-75.

[11] Augello A, De Bari C. The regulation of differentiation in mesenchymal stem cells. Hum Gene Ther. 2010;21(10): 1226-1238.

[12] Chen Y, Alman BA. Wnt pathway, an essential role in bone regeneration. J Cell Biochem. 2009;106(3):353-362.

[13] Bultink IE, Vis M, van der Horst-Bruinsma IE, et al. Inflammatory rheumatic disorders and bone. Curr Rheumatol Rep. 2012;14(3):224-230.

[14] Krause U, Gregory CA. Potential of modulating Wnt signaling pathway toward the development of bone anabolic agent. Curr Mol Pharmacol. 2012;5(2):164-173.

[15] MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17(1):9-26.

[16] Cadigan KM, Liu YI. Wnt signaling: complexity at the surface. J Cell Sci. 2006;119(Pt 3):395-402.

[17] 许兵,刘慧,许应星,等.成骨细胞中经典Wnt/β-catenin通路研究进展[J].生命科学, 2011, 23(5):477-481.

[18] 张山山,杨乃龙,徐丽丽,等.尿酸对人骨髓间充质干细胞成骨分化中Cbfα1/Runx2表达的影响[J].中国骨质疏松杂志,2013,19(4): 363-366.

[19] 杨乃龙,朱晓琳,张冬.不同浓度尿酸对人骨髓间充质干细胞增殖的影响[J].中华临床医师杂志,2012,6(17):5145-5148.

[20] 中华医学会骨质疏松和骨矿盐疾病分会.原发性骨质疏松症诊治指南(2011年)[J].中华骨质疏松和骨矿盐疾病杂志,2011,4(1): 2-17.

[21] 罗树君,曾荣,胡资兵.骨质疏松症的药物治疗进展[J].中国当代医药,2012,19(18):14-15.

[22] Nuttall ME, Gimble JM. Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol. 2004;4(3): 290-294.

[23] Clabaut A, Delplace S, Chauveau C, et al. Human osteoblasts derived from mesenchymal stem cells express adipogenic markers upon coculture with bone marrow adipocytes. Differentiation. 2010;80(1):40-45.

[24] Angers S, Moon RT. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009;10(7):468-477.

[25] Geng X, Xiao L, Lin GF, et al. Lef/Tcf-dependent Wnt/beta-catenin signaling during Xenopus axis specification. FEBS Lett. 2003;547(1-3):1-6.

[26] Lee PN, Pang K, Matus DQ, et al. A WNT of things to come: evolution of Wnt signaling and polarity in cnidarians. Semin Cell Dev Biol. 2006;17(2):157-167.

[27] Zhou H, Mak W, Zheng Y, et al. Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through Wnt signaling. J Biol Chem. 2008;283(4):1936-1945.

[28] Liu B,Tang J,Li SY,et al.Involvement of the Wnt signaling pathway and cell apoptosis in the rat hippocampus following cerebral ischemia/reperfusion injury.Neural Regen Res. 2013; 8(1): 70-75.

[29] Jullien N, Maudinet A, Leloutre B, et al. Downregulation of ErbB3 by Wnt3a contributes to wnt-induced osteoblast differentiation in mesenchymal cells. J Cell Biochem. 2012; 113(6):2047-2056.

[30] Tokuda H, Adachi S, Matsushima-Nishiwaki R, et al. Enhancement of basic fibroblast growth factor-stimulated VEGF synthesis by Wnt3a in osteoblasts. Int J Mol Med. 2011;27(6):859-864.

[31] Li HX, Luo X, Liu RX, et al. Roles of Wnt/beta-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells. Mol Cell Endocrinol. 2008;291(1-2):116-124.

[32] Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116(5):1202-1209.

[33] Holmen SL, Zylstra CR, Mukherjee A, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005; 280(22):21162-21168.

[34] Mbalaviele G, Sheikh S, Stains JP, et al. Beta-catenin and BMP-2 synergize to promote osteoblast differentiation and new bone formation. J Cell Biochem. 2005;94(2):403-418.

[35] Deschaseaux F, Sensébé L, Heymann D. Mechanisms of bone repair and regeneration. Trends Mol Med. 2009;15(9): 417-429.