Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December 2012 Volume 30 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December 2012 Volume 30 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model

  • Authors:
    • Desheng Chen
    • Xianlong Zhang
    • Yongyuan Guo
    • Sifeng Shi
    • Xin Mao
    • Xiaoyun Pan
    • Tao Cheng
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China
  • Pages: 1417-1423
    |
    Published online on: October 1, 2012
       https://doi.org/10.3892/ijmm.2012.1145
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Wear debris-induced osteolysis in periprosthetic tissue with aseptic loosening is a serious problem after total joint arthroplasty. Matrix metalloproteinase-9 (MMP-9) is expressed in osteoclast cells that surround loosening peri-implant tissue, but the molecular mechanism of MMP-9 action in wear debris-induced osteolysis remains ambiguous. We used a murine osteolysis model to examine the hypothesis that administration of an MMP-9 inhibitor reduces the expression of receptor activator of nuclear factor-κB (RANK) and nuclear factor-κB ligand (RANKL) and, thereby, suppressesdebris-induced inflammatory osteolysis. Experiments were performed in 3 groups of 15 mice: a control, a titanium (Ti) and a Ti plus tetracycline group. To provoke inflammatory osteolysis, calvarial bone was implanted from syngeneic littermates, followed by injection of Ti particles into established air pouches for all groups except the control. Tetracycline was administered daily by intraperitoneal (i.p.) injection, and PBS was administered by i.p. injection to the control and Ti groups. Mice were sacrificed 14 days after bone-Ti implantation. Pouch membranes with the intact bone implants were collected for histological and molecular analysis. Tetracycline had minimum effect on the expression of MMP-9 and tumor necrosis factor-α (TNF-α) but it decreased gene activation and inhibited the expression of RANK and RANKL, thereby inhibiting Ti-particle-induced inflammatory osteolysis. Tetracycline decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the pouch tissues. Our results in the murine osteolysis model suggest that through the downregulation of RANK/RANKL, tetracycline significantly inhibits debris-induced inflammatory osteolysis. Its use in clinical practice may help prevent complications experienced by patients who have undergone total joint arthroplasty.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1. 

SM HorowitzSB DotyJM LaneAH BursteinStudies of the mechanism by which the mechanical failure of polymethylmethacrylate leads to bone resorptionJ Bone Joint Surg Am7580281319938314821

2. 

WH HarrisWear and periprosthetic osteolysis: the problemClin Orthop Relat Res6670200110.1097/00003086-200112000-00007

3. 

E InghamJ FisherThe role of macrophages in osteolysis of total joint replacementBiomaterials2612711286200510.1016/j.biomaterials.2004.04.03515475057

4. 

G HoltC MurnaghanJ ReillyRM MeekThe biology of aseptic osteolysisClin Orthop Relat Res460240252200717620815

5. 

F von KnochC WedemeyerA HeckeleiPromotion of bone formation by simvastatin in polyethylene particle-induced osteolysisBiomaterials2657835789200515869791

6. 

X PengK TaoT ChengJ ZhuX ZhangEfficient inhibition of wear debris-induced inflammation by locally delivered siRNABiochem Biophys Res Commun377532537200810.1016/j.bbrc.2008.10.02618930023

7. 

M TakagiYT KonttinenS SantavirtaExtracellular matrix metalloproteinases around loose total hip prosthesesActa Orthop Scand65281286199410.3109/174536794089954548042479

8. 

B NawrockiM PoletteH BurletP BirembautJJ AdnetExpression of gelatinase A and its activator MT1-MMP in the inflammatory periprosthetic response to polyethyleneJ Bone Miner Res14288294199910.1359/jbmr.1999.14.2.2889933484

9. 

I TakeiM TakagiS SantavirtaMatrix metalloproteinases and tissue inhibitors of metalloproteinases in joint fluid of the patients with loose artificial hip jointsJ Biomed Mater Res45175183199910.1002/(SICI)1097-4636(19990605)45:3%3C175::AID-JBM3%3E3.0.CO;2-910397973

10. 

S WagnerH GollwitzerD WernickeR LangerKA SiebenrockW HofstetterInterface membrane fibroblasts around aseptically loosened endoprostheses express MMP-13J Orthop Res26143152200810.1002/jor.2049417853491

11. 

P ReponenC SahlbergC MunautI ThesleffK TryggvasonHigh expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse developmentJ Cell Biol12410911102199410.1083/jcb.124.6.10918132709

12. 

CH TsaiYJ ChenFM HuangYF SuYC ChangThe upregulation of matrix metalloproteinase-9 in inflamed human dental pulpsJ Endod31860862200510.1097/01.don.0000164851.55389.4e16306818

13. 

AL WucherpfennigYP LiWG Stetler-StevensonAE RosenbergP StashenkoExpression of 92 kD type IV collagenase/gelatinase B in human osteoclastsJ Bone Miner Res9549556199410.1002/jbmr.56500904158030443

14. 

PT De JongW TigchelaarCJ Van NoordenHM Van der VisPolyethylene wear particles do not induce inflammation or gelatinase (MMP-2 and MMP-9) activity in fibrous tissue interfaces of loosening total hip arthroplastiesActa Histochem113556563201120656340

15. 

C ZhangTT TangWP RenXL ZhangKR DaiInhibiting wear particle-induced osteolysis with doxycyclineActa Pharmacol Sin2816031610200710.1111/j.1745-7254.2007.00638.x17883947

16. 

Y GuHM LeeT SorsaSR SimonLM GolubDoxycycline inhibits mononuclear cell-mediated connective tissue breakdownFEMS Immunol Med Microbiol58218225201010.1111/j.1574-695X.2009.00625.x19909341

17. 

D GengY XuH YangProtection against titanium particle induced osteolysis by cannabinoid receptor 2 selective antagonistBiomaterials3119962000201010.1016/j.biomaterials.2009.11.06920004468

18. 

CA HoldingDM FindlayR StamenkovThe correlation of RANK, RANKL and TNFalpha expression with bone loss volume and polyethylene wear debris around hip implantsBiomaterials2752125219200616806459

19. 

C WedemeyerC NeuerburgA PfeifferPolyethylene particle-induced bone resorption in alpha-calcitonin gene-related peptide-deficient miceJ Bone Miner Res2210111019200710.1359/jbmr.07040817419680

20. 

SY YangB WuL MaytonProtective effects of IL-1Ra or vIL-10 gene transfer on a murine model of wear debris-induced osteolysisGene Ther11483491200410.1038/sj.gt.330219214724688

21. 

W RenSY YangPH WooleyA novel murine model of orthopaedic wear-debris associated osteolysisScand J Rheumatol33349357200410.1080/0300974041000594415513686

22. 

X MaoX PanS ZhaoX PengT ChengX ZhangProtection against titanium particle-induced inflammatory osteolysis by the proteasome inhibitor bortezomib in vivoInflammation3513781391201210.1007/s10753-012-9451-822391745

23. 

PH WooleyR MorrenJ AndaryInflammatory responses to orthopaedic biomaterials in the murine air pouchBiomaterials23517526200210.1016/S0142-9612(01)00134-X11761173

24. 

JD SamsJC MilbrandtJM FroelichAD RainvilleDG AllanHospital outcome after emergent vs elective revision total hip arthroplastyJ Arthroplasty25826828201010.1016/j.arth.2010.01.09720378305

25. 

NJ EpsteinBA WarmeJ SpanogleInterleukin-1 modulates periprosthetic tissue formation in an intramedullary model of particle-induced inflammationJ Orthop Res23501510200510.1016/j.orthres.2004.10.00415885468

26. 

J WaddellKP PritzkerEL BoyntonIncreased cytokine secretion in patients with failed implants compared with patients with primary implantsClin Orthop Relat Res434170176200510.1097/01.blo.0000155079.29604.d415864048

27. 

RM AtkinsVG LangkamerMJ PerryCJ ElsonCM CollinsBone-membrane interface in aseptic loosening of total joint arthroplastiesJ Arthroplasty12461464199710.1016/S0883-5403(97)90203-59195323

28. 

SB GoodmanP HuieY SongCellular profile and cytokine production at prosthetic interfaces. Study of tissues retrieved from revised hip and knee replacementsJ Bone Joint Surg Br80531539199810.1302/0301-620X.80B3.81589619952

29. 

SR GoldringAL SchillerM RoelkeCM RourkeDA O’NeilWH HarrisThe synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysisJ Bone Joint Surg Am6557558419836304106

30. 

KJ KimHE RubashSC WilsonJA D’AntonioEJ McClainA histologic and biochemical comparison of the interface tissues in cementless and cemented hip prosthesesClin Orthop Relat Res28714215219938448933

31. 

GF MaA AliN VerzijlIncreased collagen degradation around loosened total hip replacement implantsArthritis Rheum5429282933200610.1002/art.2206416948130

32. 

Y YokohamaT MatsumotoM HirakawaProduction of matrix metalloproteinases at the bone-implant interface in loose total hip replacementsLab Invest7389991119958558853

33. 

F VelardD Laurent-MaquinJ BrauxThe effect of zinc on hydroxyapatite-mediated activation of human polymorphonuclear neutrophils and bone implant-associated acute inflammationBiomaterials3120012009201010.1016/j.biomaterials.2009.11.066

34. 

M TakagiY TamakiH HasegawaToll-like receptors in the interface membrane around loosening total hip replacement implantsJ Biomed Mater Res A8110171026200710.1002/jbm.a.3123517415764

35. 

P LaquerriereA Grandjean-LaquerriereS Addadi-RebbahMMP-2, MMP-9 and their inhibitors TIMP-2 and TIMP-1 production by human monocytes in vitro in the presence of different forms of hydroxyapatite particlesBiomaterials2525152524200410.1016/j.biomaterials.2003.09.03414751736

36. 

N TakiJM TatroR LoweVM GoldbergEM GreenfieldComparison of the roles of IL-1, IL-6, and TNFalpha in cell culture and murine models of aseptic looseningBone4012761283200710.1016/j.bone.2006.12.05317236833

37. 

TJ FedericiThe non-antibiotic properties of tetracyclines: clinical potential in ophthalmic diseasePharmacol Res64614623201110.1016/j.phrs.2011.06.01321843641

38. 

AC LauTT DuongS ItoGJ WilsonRS YeungInhibition of matrix metalloproteinase-9 activity improves coronary outcome in an animal model of Kawasaki diseaseClin Exp Immunol157300309200910.1111/j.1365-2249.2009.03949.x19604270

39. 

S SamtaniJ AmaralMM CamposRN FarissSP BecerraDoxycycline-mediated inhibition of choroidal neovascularizationInvest Ophthalmol Vis Sci5050985106200910.1167/iovs.08-317419516001

40. 

WP RenDC MarkelR ZhangAssociation between UHMWPE particle-induced inflammatory osteoclastogenesis and expression of RANKL, VEGF, and Flt-1 in vivoBiomaterials2751615169200610.1016/j.biomaterials.2006.04.00416814378

41. 

JJ HyunHJ ChunB KeumEffect of omeprazole on the expression of transcription factors in osteoclasts and osteoblastsInt J Mol Med26877883201021042782

42. 

W SriarjK AokiK OhyaY TakagiH ShimokawaBovine dentine organic matrix down-regulates osteoclast activityJ Bone Miner Metab27315323200910.1007/s00774-009-0063-919296049

43. 

SK TatJP PelletierF MineauJ CaronJ Martel-PelletierStrontium ranelate inhibits key factors affecting bone remodeling in human osteoarthritic subchondral bone osteoblastsBone49559567201110.1016/j.bone.2011.06.00521700005

44. 

MG ChoiHS KohD KluessEffects of titanium particle size on osteoblast functions in vitro and in vivoProc Natl Acad Sci USA10245784583200510.1073/pnas.050069310215755807

45. 

S JuradoN Garcia-GiraltA Diez-PerezEffect of IL-1beta, PGE(2), and TGF-beta1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblastsJ Cell Biochem110304310201020225238

46. 

K SundaramR NishimuraJ SennRF YoussefSD LondonSV ReddyRANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiationExp Cell Res313168178200710.1016/j.yexcr.2006.10.00117084841

47. 

X MaoX PanT ChengX ZhangTherapeutic potential of the proteasome inhibitor bortezomib on titanium particle-induced inflammation in a murine modelInflammation35905912201210.1007/s10753-011-9392-721965047

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen D, Zhang X, Guo Y, Shi S, Mao X, Pan X and Cheng T: MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model. Int J Mol Med 30: 1417-1423, 2012.
APA
Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X., & Cheng, T. (2012). MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model. International Journal of Molecular Medicine, 30, 1417-1423. https://doi.org/10.3892/ijmm.2012.1145
MLA
Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X., Cheng, T."MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model". International Journal of Molecular Medicine 30.6 (2012): 1417-1423.
Chicago
Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X., Cheng, T."MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model". International Journal of Molecular Medicine 30, no. 6 (2012): 1417-1423. https://doi.org/10.3892/ijmm.2012.1145
Copy and paste a formatted citation
x
Spandidos Publications style
Chen D, Zhang X, Guo Y, Shi S, Mao X, Pan X and Cheng T: MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model. Int J Mol Med 30: 1417-1423, 2012.
APA
Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X., & Cheng, T. (2012). MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model. International Journal of Molecular Medicine, 30, 1417-1423. https://doi.org/10.3892/ijmm.2012.1145
MLA
Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X., Cheng, T."MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model". International Journal of Molecular Medicine 30.6 (2012): 1417-1423.
Chicago
Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X., Cheng, T."MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model". International Journal of Molecular Medicine 30, no. 6 (2012): 1417-1423. https://doi.org/10.3892/ijmm.2012.1145
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team