Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Xiong,Mingyue; Liu,Liqiang; Liu,Zhenhui; Gao,Hangfei

doi:10.3892/mmr.2015.4088

Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Authors:
- Mingyue Xiong
- Liqiang Liu
- Zhenhui Liu
- Hangfei Gao
View Affiliations

Affiliations: Department of Traumatic Surgery, Xinqu Hospital, The First Affiliated Hospital of Henan University of Science Technology, Luoyang, Henan 471000, P.R. China
Published online on: July 17, 2015 https://doi.org/10.3892/mmr.2015.4088
Pages: 5286-5292

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoporosis and diabetes have become serious health problems worldwide. Previous studies have suggested that diabetes is associated with osteoporosis and increased fracture risk. However, the mechanism underlying diabetes‑induced osteoporosis remains to be elucidated. Therefore, the present study aimed to examine the mechanism underlying diabetes‑induced osteoporosis, and determine the protective effects of zinc, which is known to be closely associated with osteoporosis and diabetes. The results of the present study demonstrated that zinc inhibited advanced glycation end product (AGE)‑induced MC3T3‑E1 cell apoptosis by attenuating the production of reactive oxygen species, inhibiting caspase‑3 and caspase‑9 activation, and inhibiting the release of cytochrome c from between the mitochondria and the cytosol. Furthermore, zinc was found to protect cells against AGE‑induced apoptosis via the mitogen‑activated protein kinase/extracellular signal‑regulated kinase and phosphoinositide 3‑kinase/AKT signaling pathways. In conclusion, these findings enable a better understanding of the mechanism underlying diabetes‑induced osteoporosis, and may indicate a novel target for its prevention and treatment.

View Figures

View References

1	Hofbauer LC, Brueck CC, Singh SK and Dobnig H: Osteoporosis in patients with diabetes mellitus. J Bone Miner Res. 22:1317–1328. 2007. View Article : Google Scholar : PubMed/NCBI
2	Das S and Crockett JC: Osteoporosis - a current view of pharmacological prevention and treatment. Drug Des Devel Ther. 7:435–448. 2013.PubMed/NCBI
3	Schousboe JT, Tanner SB and Leslie WD: Definition of osteoporosis by bone density criteria in men: Effect of using female instead of male young reference data depends on skeletal site and densitometer manufacturer. J Clin Densitom. 17:301–306. 2014. View Article : Google Scholar
4	Rachner TD, Khosla S and Hofbauer LC: Osteoporosis: Now and the future. Lancet. 377:1276–1287. 2011. View Article : Google Scholar : PubMed/NCBI
5	Montagnani A, Gonnelli S, Alessandri M and Nuti R: Osteoporosis and risk of fracture in patients with diabetes: An update. Aging Clin Exp Res. 23:84–90. 2011. View Article : Google Scholar : PubMed/NCBI
6	Lechleitner M, Pils K, Roller-Wirnsberger R, Beubler E, Gasser R, Mrak P, Hoppichler F and Pietschmann P: Diabetes and osteoporosis: Pathophysiological interactions and clinical importance for geriatric patients. Z Gerontol Geriatr. 46:390–397. 2013.In German. View Article : Google Scholar : PubMed/NCBI
7	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
8	Watanabe R and Okazaki R: Diabetes mellitus and osteoporosis. Diabetes mellitus and bone and calcium metabolism. Clin Calcium. 22:1307–1314. 2012.In Japanese. PubMed/NCBI
9	Motyl KJ, McCauley LK and McCabe LR: Amelioration of type I diabetes-induced osteoporosis by parathyroid hormone is associated with improved osteoblast survival. J Cell Physiol. 227:1326–1334. 2012. View Article : Google Scholar
10	Vlassara H and Uribarri J: Advanced glycation end products (AGE) and diabetes: Cause, effect, or both? Curr Diab Rep. 14:4532014. View Article : Google Scholar :
11	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
12	Yamaguchi M: Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem. 338:241–254. 2010. View Article : Google Scholar
13	Zhang X, Zhao Y, Chu Q, Wang ZY, Li H and Chi ZH: Zinc modulates high glucose-induced apoptosis by suppressing oxidative stress in renal tubular epithelial cells. Biol Trace Elem Res. 158:259–267. 2014. View Article : Google Scholar : PubMed/NCBI
14	Ruz M, Carrasco F, Rojas P, Codoceo J, Inostroza J, Basfi-fer K, Valencia A, Vásquez K, Galgani J, Pérez A, et al: Zinc as a potential coadjuvant in therapy for type 2 diabetes. Food Nutr Bull. 34:215–221. 2013.PubMed/NCBI
15	Ha H and Lee HB: Reactive oxygen species and matrix remodeling in diabetic kidney. J Am Soc Nephrol. 14(8 Suppl 3): S246–S249. 2003. View Article : Google Scholar : PubMed/NCBI
16	Yan YX, Gong YW, Guo Y, Lv Q, Guo C, Zhuang Y, Zhang Y, Li R and Zhang XZ: Mechanical strain regulates osteoblast proliferation through integrin-mediated ERK activation. PLoS One. 7:e357092012. View Article : Google Scholar : PubMed/NCBI
17	Bruinsma JJ, Jirakulaporn T, Muslin AJ and Kornfeld K: Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell. 2:567–578. 2002. View Article : Google Scholar : PubMed/NCBI
18	Park SJ, Kim SH, Choi HS, Rhee Y and Lim SK: Fibroblast growth factor 2-induced cytoplasmic asparaginyl-tRNA synthetase promotes survival of osteoblasts by regulating anti-apoptotic PI3K/Akt signaling. Bone. 45:994–1003. 2009. View Article : Google Scholar : PubMed/NCBI
19	Brzóska MM, Rogalska J, Galazyn-Sidorczuk M, Jurczuk M, Roszczenko A, Kulikowska-Karpińska E and Moniuszko-Jakoniuk J: Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. Toxicology. 237:89–103. 2007. View Article : Google Scholar : PubMed/NCBI
20	Gurban CV and Mederle O: The OPG/RANKL system and zinc ions are promoters of bone remodeling by osteoblast proliferation in postmenopausal osteoporosis. Rom J Morphol Embryol. 52(3 Suppl): 1113–1119. 2011.PubMed/NCBI
21	Fung EB, Kwiatkowski JL, Huang JN, Gildengorin G, King JC and Vichinsky EP: Zinc supplementation improves bone density in patients with thalassemia: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 98:960–971. 2013. View Article : Google Scholar : PubMed/NCBI
22	Kumar SD, Vijaya M, Samy RP, Dheen ST, Ren M, Watt F, Kang YJ, Bay BH and Tay SS: Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice. Free Radic Biol Med. 53:1595–1606. 2012. View Article : Google Scholar : PubMed/NCBI
23	Liang D, Yang M, Guo B, Cao J, Yang L and Guo X: Zinc upregulates the expression of osteoprotegerin in mouse osteo-blasts MC3T3-E1 through PKC/MAPK pathways. Biol Trace Elem Res. 146:340–348. 2012. View Article : Google Scholar
24	Niewoehner CB, Allen JI, Boosalis M, Levine AS and Morley JE: Role of zinc supplementation in type II diabetes mellitus. Am J Med. 81:63–68. 1986. View Article : Google Scholar : PubMed/NCBI
25	Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G and Katulanda P: Effects of zinc supplementation on diabetes mellitus: A systematic review and meta-analysis. Diabetol Metab Syndr. 4:132012. View Article : Google Scholar : PubMed/NCBI
26	Zhuang X, Pang X, Zhang W, Wu W, Zhao J, Yang H and Qu W: Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction. Life Sci. 90:131–139. 2012. View Article : Google Scholar
27	Wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G and Wheeler MB: Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol Chem. 285:33623–33631. 2010. View Article : Google Scholar : PubMed/NCBI
28	García-Pérez AI, Galeano E, Nieto E, Estañ MC and Sancho P: Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways. Leuk Res. 38:795–803. 2014. View Article : Google Scholar : PubMed/NCBI