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Aluminum Trichloride Inhibits the Rat Osteoblasts Mineralization In Vitro

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Abstract

Aluminum (Al) is an accumulative toxic metal. Excessive Al accumulation inhibits osteoblasts mineralization and induces osteoporosis. However, the inhibition mechanism of Al on the mineralization is not fully understood. Thus, in this study, the rat osteoblasts were cultured and exposed to 0 mmol L−1 (control group, CG) and 0.52 mmol L−1 aluminum trichloride (AlCl3, treatment group, TG) for 7, 14, and 21 days, respectively. We found that mineralized matrix nodules, the activity of bone alkaline phosphatase, the concentration of extracellular calcium, the mRNA expression of type-I collagen, the mRNA and protein expressions of osteopontin, osteocalcin, and bone sialoprotein were all decreased, while the concentration of extracellular phosphorus was increased in TG compared with CG with time prolonged. Taken together, these results indicated that AlCl3 inhibited osteoblasts mineralization in vitro.

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References

  1. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R (2015) Erratum to: clinician is guide to prevention and treatment of osteoporosis. Osteoporos Int 26:2045–2047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fine JP (2012) Bone-density testing interval and transition to osteoporosis in older women-NEJM. N Engl J Med 366:225–233

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gjoksi B, Ghayor C, Siegenthaler B, Ruangsawasdi N, Zenobi-Wong M, Weber FE (2015) The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis. Bone 78:114–121

    Article  CAS  PubMed  Google Scholar 

  4. Sliva VS, Goncalves PP (2014) Effect of lysine acetylsalicylate on aluminium accumulation and (Na+/K+)ATPase activity in rat brain cortex synaptosomes after aluminium ingestion. Toxicol Lett 232:167–174

    Article  Google Scholar 

  5. D’Souza SP, Vijayalaxmi KK, Naik P (2014) Assessment of genotoxicity of aluminium acetate in bone marrow, male germ cells and fetal liver cells of Swiss albino mice. Mutat Res Genet Toxicol Environ Mutagen 766:16–22

    Article  PubMed  Google Scholar 

  6. Sivakumar S, Khatiwada CP, Sivasubramanian J (2014) Studies the alterations of biochemical and mineral contents in bone tissue of Mus musculus due to aluminum toxicity and the protective action of desferrioxamine and deferiprone by FTIR, ICP-OES, SEM and XRD techniques. Spectrochim Acta A Mol Biomol Spectrosc 126:59–67

    Article  CAS  PubMed  Google Scholar 

  7. Aaseth J, Boivin G, Andersen O (2012) Osteoporosis and trace elements—an overview. J Trace Elem Med Biol 26:149–152

    Article  CAS  PubMed  Google Scholar 

  8. Crisponi G, Fanni D, Gerosa C, Nemolato S, Nurchi VM, Crespo-Alonso M, Lachowicz JI, Faa G (2013) The meaning of aluminium exposure on human health and aluminium-related diseases. Biomol Concepts 4:77–87

    Article  CAS  PubMed  Google Scholar 

  9. Rodriguez M, Felsenfeld AJ, Llach F (1990) Aluminum administration in the rat separately affects the osteoblast and bone mineralization. J Bone Miner Res 5:59–67

    Article  CAS  PubMed  Google Scholar 

  10. Cristinel ND, Guillaume M, Corneliu C, Daniel C (2013) Aluminum inhibits the growth of hydroxyapatite crystals developed on a biomimetic methacrylic polymer. J Trace Elem Med Biol 27:346–351

    Article  Google Scholar 

  11. Pinto M, Nicolete LDF, Rodrigues ES, Palma PVB, Orellana MD, Kashima S, Covas DT (2013) Overexpression of hsa-miR-125b during osteoblastic differentiation does not influence levels of Runx2, osteopontin, and ALPL gene expression. Braz J Med Biol Res 46:676–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Janckila AJ, Takahashi K, Sun SZ, Yam LT (2001) Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity. Clin Chem 47:74–80

    CAS  PubMed  Google Scholar 

  13. Lipton A (2010) Implications of bone metastases and the benefits of bone-targeted therapy. Semin Oncol 37:S15–S29

    Article  CAS  PubMed  Google Scholar 

  14. Chabas D, Baranzini SE, Mitchell D, Bermard CC, Rittling SR, Denhardt DT, Sobel RA, Lock C, Karpuj M, Pedotti R, Oksenberg JR, Steinman L (2001) The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294:1731–1735

    Article  CAS  PubMed  Google Scholar 

  15. Holm E, Aubin JE, Hunter GK, Beier F, Goldberg HA (2015) Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization. Bone 71:145–154

    Article  CAS  PubMed  Google Scholar 

  16. Matsuda S, Silva TL, Buzalaf MA, Rodrigues AC, De Oliveira RC (2014) Differential effects of fluoride during osteoblasts mineralization in C57BL/6J and C3H/HeJ inbred strains of mice. Biol Trace Elem Res 161:123–129

    Article  CAS  PubMed  Google Scholar 

  17. Johnson MG, Kristianto J, Yuan B, Konicke K, Blank R (2014) Big endothelin changes the cellular miRNA environment in TMOb osteoblasts and increases mineralization. Connect Tissue Res 55:113–136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun H, Hu C, Jia L, Zhu Y, Zhao H, Shao B, Wang N, Zhang Z, Li Y (2011) Effects of aluminum exposure on serum sex hormones and androgen receptor expression in male rats. Biol Trace Elem Res 144:1050–1058

    Article  CAS  PubMed  Google Scholar 

  19. Wang X, Harimoto K, Liu J, Guo J, Hinshaw S, Chang Z, Wang Z (2011) Spata4 promotes osteoblast differentiation through Erk-activated Runx2 pathway. J Bone Miner Res 26:1964–1973

    Article  CAS  PubMed  Google Scholar 

  20. Zhang X, Yang M, Lin L, Chen P, Ma KT, Zhou CY, Ao YF (2006) Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose-derived stem cells in vitro and in vivo. Calcif Tissue Int 79:169–178

    Article  CAS  PubMed  Google Scholar 

  21. Degeratu CN, Mabilleau G, Cincu C, Chappard D (2013) Aluminum inhibits the growth of hydroxyapatite crystals developed on a biomimetic methacrylic polymer. J Trace Elem Med Biol 27:346–351

    Article  CAS  PubMed  Google Scholar 

  22. Coe FL, Evan A, Worcester E (2005) Kidney stone disease. J Clin Investig 115:2598–2608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bellows CG, Reimers SM, Heersche JNM (1999) Expression of mRNAs for type-I collagen, bone sialoprotein, osteocalcin, and osteopontin at different stages of osteoblastic differentiation and their regulation by 1, 25 dihydroxyvitamin D3. Cell Tissue Res 297:249–259

    Article  CAS  PubMed  Google Scholar 

  24. Ahlstrom M, Pekkinen M, Riehle U, Lamberg-Allardt C (2008) Extracellular calcium regulates parathyroid hormone-related peptide expression in osteoblasts and osteoblast progenitor cells. Bone 42:483–490

    Article  CAS  PubMed  Google Scholar 

  25. Lossdörfer S, Schwartz Z, Lohmann CH, Greenspan DC, Ranly DM, Boyan BD (2004) Osteoblast response to bioactive glasses in vitro correlates with inorganic phosphate content. Biomaterials 25:2547–2555

    Article  PubMed  Google Scholar 

  26. Collin P, Nefussi JR, Wetterwald A, Nicolas V, Boy-Lefevre M, Fleisch H, Forest N (1992) Expression of collagen, osteocalcin, and bone alkaline phosphatase in a mineralizing rat osteoblastic cell culture. Calcif Tissue Int 50:175–183

    Article  CAS  PubMed  Google Scholar 

  27. Gomez BJ, Ardakani S, Ju J, Jenkins D, Cerelli MJ, Daniloff GY, Kung VT (1995) Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. Clin Chem 41:1560–1566

    CAS  PubMed  Google Scholar 

  28. Lynch MP, Stein JL, Stein GS, Lian JB (1995) The influence of type I collagen on the development and maintenance of the osteoblast phenotype in primary and passaged rat calvarial osteoblasts: modification of expression of genes supporting cell growth, adhesion, and extracellular matrix mineralization. Exp Cell Res 216:35–45

    Article  CAS  PubMed  Google Scholar 

  29. Hoyer B, Bernhardt A, Heinemann S, Stachel I, Meyer M, Gelinsky M (2012) Biomimetically mineralized salmon collagen scaffolds for application in bone tissue engineering. Biomacromolecules 13:1059–1066

    Article  CAS  PubMed  Google Scholar 

  30. Lieberherr M, Grosse B, Cournot-Witmer G, Hermann-Erlee MP, Balsan S (1987) Aluminum action on mouse bone cell metabolism and response to PTH and 1,25(OH)2D3. Kidney Int 317:36–743

    Google Scholar 

  31. Sprague SM, Krieger NS, Bushinsky DA (1993) Aluminum inhibits bone nodule formation and calcification in vitro. Am J Physiol Ren Physiol 264:F882–F890

    CAS  Google Scholar 

  32. Li XW, Han YF, Guan Y, Zhang L, Bai CS, Li YF (2012) Aluminum induces osteoblast apoptosis through the oxidative stress-mediated JNK signaling pathway. Biol Trace Elem Res 150:502–508

    Article  PubMed  Google Scholar 

  33. Gordon JAR, Tye C, Sampaio A, Underhill M, Hunter G, Goldberg H (2007) Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro. Bone 41:462–473

    Article  CAS  PubMed  Google Scholar 

  34. Taichman RS, Hauschka PV (1992) Effects of interleukin-1 beta and tumor necrosis factor-alpha on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. Inflammation 16:587–601

    Article  CAS  PubMed  Google Scholar 

  35. Gomez-Alonso C, Menendez-Rodriguez P, Virgos-Soriano MJ, Femandez-Martin JL, Fernandez-Coto MT, Cannata-Andia JB (1999) Aluminum-induced osteogenesis in osteopenic rats with normal renal function. Calcif Tissue Int 64:534–541

    Article  CAS  PubMed  Google Scholar 

  36. Fanti P, Kindy MS, Mohapatra S, Klein J, Malluche HH (2006) Dose-dependent effects of aluminum on osteocalcin synthesis in osteoblast-like ROS 17/2 cells in culture. Am J Physiol Endocrinol Metab 263:E1113–E1118

    Google Scholar 

  37. Denhardt DT, Guo X (1993) Osteopontin: a protein with diverse functions. FASEB J 7:1475–1482

    CAS  PubMed  Google Scholar 

  38. McKee MD, Nanci A (1996) Osteopontin at mineralized tissue interfaces in bone, teeth and osseointegrated implants: ultrastructral distribution and implication for mineralized tissue formation, turnover, and repair. Microsc Res Tech 33:141–164

    Article  CAS  PubMed  Google Scholar 

  39. Cho HJ, Cho HJ, Kim HS (2009) Osteopontin: a multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification. Curr Atheroscler Rep 11:206–213

    Article  CAS  PubMed  Google Scholar 

  40. Somerman MJ, Prince CW, Butler WT, Foster RA, Moehring JM, Sauk JJ (1989) Cell attachment activity of the 44 kilodalton bone phosphoprotein is not restricted to bone cells. Matrix 9:49–54

    Article  CAS  PubMed  Google Scholar 

  41. Shin H, Zygourakis K, Farach-Carson MC, et al. (2004) Attachment, proliferation, and migration of marrow stromal osteoblasts cultured on biomimetic hydrogels modified with an osteopontin-derived peptide. [J] Biomater 25(5):895–906

    Article  Google Scholar 

  42. Mosig RA, Martignetti JA (2013) Loss of MMP-2 in murine osteoblasts upregulates osteopontin and bone sialoprotein expression in a circuit regulating bone homeostasis. Dis Model Mech 6:397–403

    Article  CAS  PubMed  Google Scholar 

  43. Chen J, Singh K, Mukherjee B, Sodek J (1993) Developmental expression of osteopontin (OPN) mRNA in rat tissues: evidence for a role for OPN in bone formation and resorption. Matrix 13:113–123

    Article  CAS  PubMed  Google Scholar 

  44. Espinoza J, Sanchez M, Sanchez A, Hanna P, Torrejon M, Buisine N (2010) Two families of Xenopus tropicalis skeletal genes display well-conserved expression patterns with mammals in spite of their highly divergent regulatory regions. Evol Dev 12:541–551

    Article  CAS  PubMed  Google Scholar 

  45. Shintani S, Kamakura N, Kobata M, Toyosawa S, Onishi T, Sato A (2008) Identification and characterization of integrin-binding sialoprotein (IBSP) genes in reptile and amphibian. Gene 424:11–17

    Article  CAS  PubMed  Google Scholar 

  46. Hunter GK, Goldberg HA (1993) Nucleation of hydroxyapatite by bone sialoprotein. Proc Natl Acad Sci U S A 90:8562–8565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bernards MT, Qin C, Jiang S (2008) MC3T3-E1 cell adhesion to hydroxyapatite with adsorbed bone sialoprotein, bone osteopontin, and bovine serum albumin. Colloids Surf B: Biointerfaces 64:236–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bernards MT, Qin C, Ratner BD, Jiang S (2008) Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically bound to collagen I. J Biomed Mater Res A 86:779–787

    Article  PubMed  PubMed Central  Google Scholar 

  49. Gordon JA, Hunter GK, Goldberg HA (2009) Activation of the mitogen-activated protein kinase pathway by bone sialoprotein regulates osteoblast differentiation. Cells Tissues Organs 189:138–143

    Article  CAS  PubMed  Google Scholar 

  50. Bianco P, Fisher LW, Young MF, Termine JD, Robey PG (1991) Expression of bone sialoprotein (BSP) in developing human tissues. Calcif Tissue Int 49:421–426

    Article  CAS  PubMed  Google Scholar 

  51. Aubin JE (2001) Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2:81–94

    Article  CAS  PubMed  Google Scholar 

  52. Chen J, Shapiro HS, Sodek J (1992) Development expression of bone sialoprotein mRNA in rat mineralized connective tissues. J Bone Miner Res 7:987–997

    Article  CAS  PubMed  Google Scholar 

  53. Chen JK, Shapiro HS, Wrana JL, Reimers S, Heersche JN, Sodek J (1991) Localization of bone sialoprotein (BSP) expression to sites of mineralized tissue formation in fetal rat tissues by in situ hybridization. Matrix 11:133–143

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The study was supported by a grant from the National Science Foundation Project (31372496) and the Science Foundation for Young Scientists of Jilin Province, China (20130522091JH).

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Authors and Affiliations

  1. College of Veterinary Medicine, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin, 150030, China

    Miao Song, Hui Huo, Zheng Cao, Yanfei Han & Li Gao

  2. College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China

    Hui Huo

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  1. Miao Song
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Correspondence to Li Gao.

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Miao Song and Hui Huo contributed equally to this study.

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Song, M., Huo, H., Cao, Z. et al. Aluminum Trichloride Inhibits the Rat Osteoblasts Mineralization In Vitro. Biol Trace Elem Res 175, 186–193 (2017). https://doi.org/10.1007/s12011-016-0761-9

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  • DOI: https://doi.org/10.1007/s12011-016-0761-9

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