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International Journal of Molecular Medicine
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Article

Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells

  • Authors:
    • Nan Sun
    • Li Yang
    • Yingbin Li
    • Hua Zhang
    • Hong Chen
    • Duan Liu
    • Qingnan Li
    • Dehong Cai
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
  • Pages: 485-491
    |
    Published online on: May 30, 2013
       https://doi.org/10.3892/ijmm.2013.1402
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Abstract

Advanced oxidation protein products (AOPPs) as a novel marker of oxidative stress, are involved in a variety of diseases, including osteoporosis. Although a number of studies have shown the possible functions of AOPPs in biological processes, little is known about the role of AOPPs in the pathogenesis of osteoporosis. In this study, we aimed to investigate the effect of AOPPs on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (MSCs). MSCs, isolated from bone marrow, were cultured in the absence or presence of AOPPs (50, 100, 200 and 400 mg/ml). MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase (ALP) activity, the mRNA expression of ALP and collagen I and bone nodule formation were detected to assess osteogenic differentiation. Reactive oxygen species (ROS) generation was analyzed with the probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The expression of receptor of advanced glycation end-products (RAGE) at the mRNA and protein level was detected by real-time PCR and western blot analysis, respectively. Compared with the control group, AOPPs inhibited MSC proliferation in a dose- and time-dependent manner. Moreover, AOPPs induced a significant reduction in ALP activity, as well as a decrease in ALP and collagen I mRNA levels in the MSCs; bone nodule formation was also inhibited. Furthermore, AOPPs increased ROS generation in the MSCs, and upregulated the expression of RAGE at the mRNA and protein level. These results suggest that AOPPs inhibit the proliferation and osteogenic differentiation of MSCs, possibly through the AOPPs-RAGE-ROS pathway; this may be an important mechanism in the development of osteoporosis.
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1 

Wongdee K and Charoenphandhu N: Osteoporosis in diabetes mellitus: possible cellular and molecular mechanisms. World J Diabetes. 2:41–48. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Cervellati C, Bonaccorsi G, Cremonini E, Bergamini CM, Patella A, Castaldini C, Ferrazzini S, Capatti A, Picarelli V, Pansini FS and Massari L: Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women. Clin Chem Lab Med. 51:333–338. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Fatokun AA, Stone TW and Smith RA: Responses of differentiated MC3T3-E1 osteoblast-like cells to reactive oxygen species. Eur J Pharmacol. 587:35–41. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Sheweita SA and Khoshhal KI: Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab. 8:519–525. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P and Descamps-Latscha B: Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 49:1304–1313. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Witko-Sarsat V, Friedlander M, Nguyen Khoa T, Capeillere-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drueke T and Descamps-Latscha B: Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol. 161:2524–2532. 1998.PubMed/NCBI

7 

Guo ZJ, Niu HX, Hou FF, Zhang L, Fu N, Nagai R, Lu X, Chen BH, Shan YX, Tian JW, Nagaraj RH, Xie D and Zhang X: Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. Antioxid Redox Signal. 10:1699–1712. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Piwowar A: Advanced oxidation protein products. Part I. Mechanism of the formation, characteristics and property. Pol Merkur Lekarski. 28:166–169. 2010.(In Polish).

9 

Piwowar A, Knapik-Kordecka M and Warwas M: AOPP and its relations with selected markers of oxidative/antioxidative system in type 2 diabetes mellitus. Diabetes Res Clin Pract. 77:188–192. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Cumaoglu A, Cevik C, Rackova L, Ari N and Karasu C: Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin-diabetic rats: role of oxidative/nitrosative stress. BioFactors. 30:171–178. 2007. View Article : Google Scholar

11 

Krzystek-Korpacka M, Neubauer K, Berdowska I, Boehm D, Zielinski B, Petryszyn P, Terlecki G, Paradowski L and Gamian A: Enhanced formation of advanced oxidation protein products in IBD. Inflamm Bowel Dis. 14:794–802. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Kaneda H, Taguchi J, Ogasawara K, Aizawa T and Ohno M: Increased level of advanced oxidation protein products in patients with coronary artery disease. Atherosclerosis. 162:221–225. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Collet C, Schiltz C, Geoffroy V, Maroteaux L, Launay JM and de Vernejoul MC: The serotonin 5-HT2B receptor controls bone mass via osteoblast recruitment and proliferation. FASEB J. 22:418–427. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Zhang YB, Zhong ZM, Hou G, Jiang H and Chen JT: Involvement of oxidative stress in age-related bone loss. J Surg Res. 169:e37–e42. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Choi EM and Kim YH: Hesperetin attenuates the highly reducing sugar-triggered inhibition of osteoblast differentiation. Cell Biol Toxicol. 24:225–231. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Lee KH and Choi EM: Myricetin, a naturally occurring flavonoid, prevents 2-deoxy-D-ribose induced dysfunction and oxidative damage in osteoblastic MC3T3-E1 cells. Eur J Pharmacol. 591:1–6. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Zhong ZM, Bai L and Chen JT: Advanced oxidation protein products inhibit proliferation and differentiation of rat osteoblast-like cells via NF-kappaB pathway. Cell Physiol Biochem. 24:105–114. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Rodan GA and Martin TJ: Therapeutic approaches to bone diseases. Science. 289:1508–1514. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Long MW: Osteogenesis and bone-marrow-derived cells. Blood Cells Mol Dis. 27:677–690. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Dalle Carbonare L, Valenti MT, Zanatta M, Donatelli L and Lo Cascio V: Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis Rheum. 60:3356–3365. 2009.PubMed/NCBI

22 

Benisch P, Schilling T, Klein-Hitpass L, Frey SP, Seefried L, Raaijmakers N, Krug M, Regensburger M, Zeck S, Schinke T, Amling M, Ebert R and Jakob F: The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PloS One. 7:e451422012. View Article : Google Scholar : PubMed/NCBI

23 

Kume S, Kato S, Yamagishi S, Inagaki Y, Ueda S, Arima N, Okawa T, Kojiro M and Nagata K: Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone. J Bone Miner Res. 20:1647–1658. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Farley JR and Jorch UM: Differential effects of phospholipids on skeletal alkaline phosphatase activity in extracts, in situ and in circulation. Arch Biochem Biophys. 221:477–488. 1983. View Article : Google Scholar : PubMed/NCBI

25 

Harada S and Rodan GA: Control of osteoblast function and regulation of bone mass. Nature. 423:349–355. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Deng YQ, Fu Y, Su XP and Tang ZY: Biologic effects of advanced oxidative protein products on the human gingival fibroblasts. Zhonghua Kou Qiang Yi Xue Za Zhi. 44:270–273. 2009.(In Chinese).

27 

Ouyang P, Liu S, Bei W, Lai W, Hou F and Xu A: Effects of flavone from leaves of Diospyros kaki on adventitial fibroblasts proliferation by advanced oxidation protein products in vitro. Zhong Yao Cai. 27:186–188. 2004.(In Chinese).

28 

Siggelkow H, Rebenstorff K, Kurre W, Niedhart C, Engel I, Schulz H, Atkinson MJ and Hufner M: Development of the osteoblast phenotype in primary human osteoblasts in culture: comparison with rat calvarial cells in osteoblast differentiation. J Cell Biochem. 75:22–35. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Beck GR Jr, Sullivan EC, Moran E and Zerler B: Relationship between alkaline phosphatase levels, osteopontin expression, and mineralization in differentiating MC3T3-E1 osteoblasts. J Cell Biochem. 68:269–280. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM and Luo SQ: Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun. 314:197–207. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N and Lee SY: A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood. 106:852–859. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Barbagallo I, Vanella A, Peterson SJ, Kim DH, Tibullo D, Giallongo C, Vanella L, Parrinello N, Palumbo GA, Di Raimondo F, Abraham NG and Asprinio D: Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation. J Bone Mineral Metab. 28:276–288. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Yan SF, Ramasamy R and Schmidt AM: The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res. 106:842–853. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM and Wautier JL: Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab. 280:E685–E694. 2001.PubMed/NCBI

35 

Yamagishi S: Role of advanced glycation end products (AGEs) in osteoporosis in diabetes. Curr Drug Targets. 12:2096–2102. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Li G, Xu J and Li Z: Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling. Biochem Biophys Res Commun. 423:684–689. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Ding KH, Wang ZZ, Hamrick MW, Deng ZB, Zhou L, Kang B, Yan SL, She JX, Stern DM, Isales CM and Mi QS: Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss. Biochem Biophys Res Commun. 340:1091–1097. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sun N, Yang L, Li Y, Zhang H, Chen H, Liu D, Li Q and Cai D: Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells. Int J Mol Med 32: 485-491, 2013.
APA
Sun, N., Yang, L., Li, Y., Zhang, H., Chen, H., Liu, D. ... Cai, D. (2013). Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells. International Journal of Molecular Medicine, 32, 485-491. https://doi.org/10.3892/ijmm.2013.1402
MLA
Sun, N., Yang, L., Li, Y., Zhang, H., Chen, H., Liu, D., Li, Q., Cai, D."Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells". International Journal of Molecular Medicine 32.2 (2013): 485-491.
Chicago
Sun, N., Yang, L., Li, Y., Zhang, H., Chen, H., Liu, D., Li, Q., Cai, D."Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells". International Journal of Molecular Medicine 32, no. 2 (2013): 485-491. https://doi.org/10.3892/ijmm.2013.1402
Copy and paste a formatted citation
x
Spandidos Publications style
Sun N, Yang L, Li Y, Zhang H, Chen H, Liu D, Li Q and Cai D: Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells. Int J Mol Med 32: 485-491, 2013.
APA
Sun, N., Yang, L., Li, Y., Zhang, H., Chen, H., Liu, D. ... Cai, D. (2013). Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells. International Journal of Molecular Medicine, 32, 485-491. https://doi.org/10.3892/ijmm.2013.1402
MLA
Sun, N., Yang, L., Li, Y., Zhang, H., Chen, H., Liu, D., Li, Q., Cai, D."Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells". International Journal of Molecular Medicine 32.2 (2013): 485-491.
Chicago
Sun, N., Yang, L., Li, Y., Zhang, H., Chen, H., Liu, D., Li, Q., Cai, D."Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells". International Journal of Molecular Medicine 32, no. 2 (2013): 485-491. https://doi.org/10.3892/ijmm.2013.1402
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