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Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation

  • Authors:
    • Chaoqun Yu
    • Dong Huang
    • Kunyuan Wang
    • Bochuan Lin
    • Yuanhang Liu
    • Songbo Liu
    • Weichi Wu
    • Huiru Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Traumatology and Microsurgery, The Third Clinical College, Southern Medical University, Guangdong No. 2 Provincial People's Hospital, Guangzhou, Guangdong 510310, P.R. China, Department of Nephrology, The First Clinical College, Southern Medical University, Guangzhou, Guangdong 510310, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 543-550
    |
    Published online on: December 14, 2016
       https://doi.org/10.3892/mmr.2016.6047
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Abstract

Advanced oxidation protein products (AOPPs) are recognized as novel markers of oxidative stress and contribute to various medical conditions, which are associated with secondary osteoporosis. However, little is currently known regarding the role of AOPPs in the development of secondary osteoporosis. As the commander cells of bone remodeling, osteocytes are involved in the pathogenesis of osteoporosis. The present study aimed to determine the cytotoxic mechanisms of AOPPs on osteocytic MLO‑Y4 cells. The results demonstrated that treatment with AOPPs significantly triggered apoptosis of MLO‑Y4 cells, in a dose‑ and time‑dependent manner. Furthermore, exposure to AOPPs induced phosphorylation of c‑Jun N‑terminal kinases (JNK) and p38 mitogen‑activated protein kinases (MAPK). Conversely, N‑acetylcysteine inhibited the activation of JNK and p38 MAPK, thus suggesting that the AOPPs‑induced activation of JNK/p38 MAPK is reactive oxygen species (ROS)‑dependent. In addition, SB203580 and SP600125 suppressed apoptosis, but did not affect ROS production, following AOPPs treatment. Notably, AOPPs also induced a significant upregulation in the expression levels of sclerostin and receptor activator of nuclear factor kappa‑B ligand (RANKL) in a JNK/p38 MAPK-dependent manner. These findings provide novel insights into the molecular mechanisms underlying AOPPs‑mediated cell death, and suggest that modulation of apoptotic pathways via the MAPK signaling cascade may be considered a therapeutic strategy for the prevention and treatment of secondary osteoporosis.
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1 

Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, 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

2 

Witko-Sarsat V, Friedlander M, Khoa T Nguyen, Capeillère-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drüeke T and Descamps-Latscha B: Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure1, 2. J Immunol. 161:2524–2532. 1998.PubMed/NCBI

3 

Tucker PS, Dalbo VJ, Han T and Kingsley MI: Clinical and research markers of oxidative stress in chronic kidney disease. Biomarkers. 18:103–115. 2013. View Article : Google Scholar : PubMed/NCBI

4 

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

5 

Baskol G, Demir H, Baskol M, Kilic E, Ates F, Karakukcu C and Ustdal M: Investigation of protein oxidation and lipid peroxidation in patients with rheumatoid arthritis. Cell Biochem Funct. 24:307–311. 2006. View Article : Google Scholar : PubMed/NCBI

6 

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

7 

Painter SE, Kleerekoper M and Camacho PM: Secondary osteoporosis: A review of the recent evidence. Endocr Pract. 12:436–445. 2006. View Article : Google Scholar : PubMed/NCBI

8 

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 Physol Biochem. 24:105–114. 2009. View Article : Google Scholar

9 

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.PubMed/NCBI

10 

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, et al: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 95:3597–3602. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, et al: Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 17:1231–1234. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Semenov M, Tamai K and Xi H: SOST is a ligand for LRP5/LRP6 and a wnt signaling inhibitor. J Biol Chem. 280:26770–26775. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Krause C, Korchynskyi O, de Rooij K, Weidauer SE, de Gorter DJ, van Bezooijen RL, Hatsell S, Economides AN, Mueller TD, Löwik CW and ten Dijke P: Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. J Biol Chem. 285:41614–41626. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI

15 

Reddy KB, Nabha SM and Atanaskova N: Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 22:395–403. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Burotto M, Chiou VL, Lee JM and Kohn EC: The MAPK pathway across different malignancies: A new perspective. Cancer. 120:3446–3456. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Thouverey C and Caverzasio J: Focus on the p38 MAPK signaling pathway in bone development and maintenance. Bonekey Rep. 4:7112015. View Article : Google Scholar : PubMed/NCBI

19 

Wang SS, Huang QT, Zhong M and Yin Q: AOPPs (advanced oxidation protein products) promote apoptosis in trophoblastic cells through interference with NADPH oxidase signaling: Implications for preeclampsia. J Matern Fetal Neonatal Med. 28:1747–1755. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Zhou LL, Cao W, Xie C, Tian J, Zhou Z, Zhou Q, Zhu P, Li A, Liu Y, Miyata T, et al: The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis. Kidney Int. 82:759–770. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Xie F, Sun S, Xu A, Zheng S, Xue M, Wu P, Zeng JH and Bai L: Advanced oxidation protein products induce intestine epithelial cell death through a redox-dependent, c-jun N-terminal kinase and poly (ADP-ribose) polymerase-1-mediated pathway. Cell Death Dis. 5:e10062014. View Article : Google Scholar : PubMed/NCBI

22 

Bonewald LF: The amazing osteocyte. J Bone Res. 26:229–238. 2011. View Article : Google Scholar

23 

Compton JT and Lee FY: A review of osteocyte function and the emerging importance of sclerostin. J Bone Joint Surg Am. 96:1659–1668. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Seibel MJ, Cooper MS and Zhou H: Glucocorticoid-induced osteoporosis: Mechanisms, management and future perspectives. Lancet Diabetes Endocrinol. 1:59–70. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Osone S, Hosoi H, Kuwahara Y, Matsumoto Y, Iehara T and Sugimoto T: Fenretinide induces sustained-activation of JNK/p38 MAPK and apoptosis in a reactive oxygen species-dependent manner in neuroblastoma cells. Int J Cancer. 112:219–224. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Park GB, Choi Y, Kim YS, Lee HK, Kim D and Hur DY: ROS-mediated JNK/p38-MAPK activation regulates bax translocation in sorafenib-induced apoptosis of EBV-transformed B cells. Int J Oncol. 44:977–985. 2014.PubMed/NCBI

27 

Lee SY, Kang SU, Kim KI, Kang S, Shin YS, Chang JW, Yang SS, Lee K, Lee JS, Moon E and Kim CH: Nonthermal plasma induces apoptosis in ATC cells: Involvement of JNK and p38 MAPK-dependent ROS. Yonsei Med J. 55:1640–1647. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Palit S, Kar S, Sharma G and Das PK: Hesperetin induces apoptosis in breast carcinoma by triggering accumulation of Ros and activation of ASK1/JNK Pathway. J Cell Physiol. 230:1729–1739. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, et al: Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 22:6267–6276. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM and Atkins GJ: Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PloS one. 6:e259002011. View Article : Google Scholar : PubMed/NCBI

31 

Kostenuik PJ, Smith SY, Jolette J, Schroeder J, Pyrah I and Ominsky MS: Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody. Bone. 49:151–161. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu C, Huang D, Wang K, Lin B, Liu Y, Liu S, Wu W and Zhang H: Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation. Mol Med Rep 15: 543-550, 2017.
APA
Yu, C., Huang, D., Wang, K., Lin, B., Liu, Y., Liu, S. ... Zhang, H. (2017). Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation. Molecular Medicine Reports, 15, 543-550. https://doi.org/10.3892/mmr.2016.6047
MLA
Yu, C., Huang, D., Wang, K., Lin, B., Liu, Y., Liu, S., Wu, W., Zhang, H."Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation". Molecular Medicine Reports 15.2 (2017): 543-550.
Chicago
Yu, C., Huang, D., Wang, K., Lin, B., Liu, Y., Liu, S., Wu, W., Zhang, H."Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation". Molecular Medicine Reports 15, no. 2 (2017): 543-550. https://doi.org/10.3892/mmr.2016.6047
Copy and paste a formatted citation
x
Spandidos Publications style
Yu C, Huang D, Wang K, Lin B, Liu Y, Liu S, Wu W and Zhang H: Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation. Mol Med Rep 15: 543-550, 2017.
APA
Yu, C., Huang, D., Wang, K., Lin, B., Liu, Y., Liu, S. ... Zhang, H. (2017). Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation. Molecular Medicine Reports, 15, 543-550. https://doi.org/10.3892/mmr.2016.6047
MLA
Yu, C., Huang, D., Wang, K., Lin, B., Liu, Y., Liu, S., Wu, W., Zhang, H."Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation". Molecular Medicine Reports 15.2 (2017): 543-550.
Chicago
Yu, C., Huang, D., Wang, K., Lin, B., Liu, Y., Liu, S., Wu, W., Zhang, H."Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation". Molecular Medicine Reports 15, no. 2 (2017): 543-550. https://doi.org/10.3892/mmr.2016.6047
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