Skip to main content

Advertisement

Log in

Omega-3 and Omega-6 Fatty Acids Act as Inhibitors of the Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity

  • Published:
The Protein Journal Aims and scope Submit manuscript

Abstract

Polyunsaturated fatty acids have been reported to play a protective role in a wide range of diseases characterized by an increased metalloproteinases (MMPs) activity. The recent finding that omega-3 and omega-6 fatty acids exert an anti-inflammatory effect in periodontal diseases has stimulated the present study, designed to determine whether such properties derive from a direct inhibitory action of these compounds on the activity of MMPs. To this issue, we investigated the effect exerted by omega-3 and omega-6 fatty acids on the activity of MMP-2 and MMP-9, two enzymes that actively participate to the destruction of the organic matrix of dentin following demineralization operated by bacteria acids. Data obtained (both in vitro and on ex-vivo teeth) reveal that omega-3 and omega-6 fatty acids inhibit the proteolytic activity of MMP-2 and MMP-9, two enzymes present in dentin. This observation is of interest since it assigns to these compounds a key role as MMPs inhibitors, and stimulates further study to better define their therapeutic potentialities in carious decay.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MMP-2:

Matrix metalloproteinase 2

MMP-9:

Matrix metalloproteinase-9

FE-SEM:

Field emission scanning electron microscope

DHA:

Docosahexaenoic acid

References

  1. Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207–214

    Article  CAS  Google Scholar 

  2. Malemud CJ (2006) Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci 11:1696–1701

    Article  CAS  Google Scholar 

  3. Visse R, Nagase H (2003) Matrix proteinases and tissue inhibitors of metalloproteinases: structure, function and biochemistry. Circ Res 92:827–839

    Article  CAS  Google Scholar 

  4. Gaide Chevronnay HP, Selvais C, Emonard H, Galant C, Marbaix E, Henriet P (2012) Regulation of matrix metalloproteinases activity studied in human endometrium as a paradigm of cyclic tissue breakdown and regeneration. Biochim Biophys Acta 1824:146–156

    Article  CAS  Google Scholar 

  5. Chen Q, Jin M, Yang F, Zhu J, Xiao Q, Zhang L (2013) Matrix metalloproteinases: inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators Inflamm 2013:928315

    Google Scholar 

  6. Lukaszewicz-Zając M, Mroczko B, Kornhuber J, Lewczuk P (2014) Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) in the tumors of central nervous system (CNS). J Neural Transm 121:469–477

    Article  Google Scholar 

  7. Ulasov I, Yi R, Guo D, Sarvaiya P, Cobbs C (2014) The emerging role of MMP-14 in brain tumorigenesis and future therapeutics. Biochim Biophys Acta 1846:113–120

    CAS  Google Scholar 

  8. Tauro M, McGuire J, Lynch CC (2014) New approaches to selectively target cancer-associated matrix metalloproteinase activity. Cancer Metastasis Rev 33:1043–1057

    Article  CAS  Google Scholar 

  9. Wei J, Richbourgh B, Jia T, Liu C (2014) ADAMTS-12: a multifaced metalloproteinase in arthritis and inflammation. Mediators Inflamm 2014:649718

    Google Scholar 

  10. Singh D, Srivastava SK, Chaudhuri TK, Upadhyay G (2015) Multifaced role of matrix metalloproteinases (MMPs). Front Mol Biosci 13:2–19

    Google Scholar 

  11. Wall R, Ross RP, Fitzgerald GF, Stanton C (2010) Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 68:280–289

    Article  Google Scholar 

  12. Marion-Letellier R, Butler M, Déchelotte P, Playford RJ, Ghosh S (2008) Comparison of cytokine modulation by natural peroxisome proliferator-activated receptor gamma ligands with synthetic ligands in intestinal-like Caco-2 cells and human dendritic cells-potential for dietary modulation of peroxisome proliferator-activated receptor gamma in intestinal inflammation. Am J Clin Nutr 87:939–994

    CAS  Google Scholar 

  13. Fetterman JW Jr, Zdanowicz MM (2009) Therapeutic potential of n-3 polyunsaturated fatty acids in disease. Am J Health Syst Pharm 66:1169–1179

    Article  CAS  Google Scholar 

  14. Siddiqui RA, Harvey KA, Xu Z, Bammerlin EM, Walker C, Altenburg JD (2011) Docosahexaenoic acid: a natural powerful adjuvant that improves efficacy for anticancer treatment with no adverse effects. Biofactors 37:399–412

    Article  CAS  Google Scholar 

  15. Harris WS, Dayspring TD, Moran TJ (2013) Omega-3 fatty acids and cardiovascular disease: new developments and applications. Postgrad Med 125:100–113

    Article  Google Scholar 

  16. Haast RA, Kiliaan AJ (2015) Impact of fatty acids on brain circulation, structure and function. Prostaglandins Leukot Essent Fatty Acids 92:3–14

    Article  CAS  Google Scholar 

  17. Xu Y, Qian SY (2014) Anti-cancer activities of ω-6 polyunsaturated fatty acids. Biomed J 37:112–119

    Article  Google Scholar 

  18. Schmitz G, Ecker J (2008) The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 47:147–155

    Article  CAS  Google Scholar 

  19. Simopoulos AP (2008) The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med 233:674–688

    Article  CAS  Google Scholar 

  20. Sakai M, Kakutani S, Horikawa C, Tokuda H, Kawashima H, Shibata H, Okubo H, Sasaki S (2012) Arachidonic acid and cancer risk: a systematic review of observational studies. BMC Cancer 12:606

    Article  CAS  Google Scholar 

  21. Hulbert AJ, Turner N, Storlien LH, Else PL (2005) Dietary fats and membrane function: implications for metabolism and disease. Biol Rev Camb Philos Soc 80:155–169

    Article  CAS  Google Scholar 

  22. Das UN (2006) Essential Fatty acids—a review. Curr Pharm Biotechnol 7:467–482

    Article  CAS  Google Scholar 

  23. Calder PC (2015) Functional roles of fatty acids and their effects on human health. JPEN J Parenter Enteral Nutr 39(1):18S–32 S

    Article  Google Scholar 

  24. Russo GL (2009) Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 77:937–946

    Article  CAS  Google Scholar 

  25. Mazzoni A, Mannello F, Tay FR, Tonti GA, Papa S, Mazzotti G, Di Lenarda R, Pashley DH, Breschi L (2007) Zymographic analysis and characterization of MMP-2 and -9 forms in human sound dentin. J Dent Res 86:436–440

    Article  CAS  Google Scholar 

  26. Santos J, Carrilho M, Tervahartiala T, Sorsa T, Breschi L, Mazzoni A, Pashley D, Tay F, Ferraz C, Tjäderhane L (2009) Determination of matrix metalloproteins in human radicular dentin. J Endod 35:686–689

    Article  Google Scholar 

  27. Shimada Y, Ichinose S, Sadr A, Burrow MF, Tagami J (2009) Localization of matrix metalloproteinases (MMPs-2, 8, 9 and 20) in normal and carious dentine. Aust Dent J 54:347–354

    Article  CAS  Google Scholar 

  28. Van Stijp AJP, Jansen DC, DeGroot J, ten Cate JM, Everts V (2003) Host-derived proteinases and degradation of dentine collagen in situ. Caries Res 37:58–65

    Article  Google Scholar 

  29. Buzalaf MA, Kato MT, Hannas AR (2012) The role of matrix metalloproteinases in dental erosion. Adv Dent Res 24:72–76

    Article  CAS  Google Scholar 

  30. Chaussain C, Boukpessi T, Khaddam M, Tjaderhane L, George A, Menashi S (2013) Dentin matrix degradation by host matrix metalloproteinases: inhibition and clinical perspectives toward regeneration. Front Physiol 4:308

    Article  Google Scholar 

  31. Tjäderhane L, Nascimento FD, Breschi L, Mazzoni A, Tersariol IL, Geraldeli S, Tezvergil-Mutluay A, Carrilho M, Carvalho RM, Tay FR, Pashley DH (2013) Optimizing dentin bond durability: control of collagen degradation by matrix metalloproteinases and cysteine cathepsins. Dent Mater 29:116–135

    Article  Google Scholar 

  32. Vidal CM, Tjäderhane L, Scaffa PM, Tersariol IL, Pashley D, Nader HB, Nascimento FD, Carrilho MR (2014) Abundance of MMPs and cysteine cathepsins in caries-affected dentin. J Dent Res 93:269–274

    Article  CAS  Google Scholar 

  33. Mazzoni A, Tjäderhane L, Checchi V, Di Lenarda R, Salo T, Tay FR, Pashley DH, Breschi L (2015) Role of dentin MMPs in caries progression and bond stability. J Dent Res 94:241–251

    Article  CAS  Google Scholar 

  34. Carrilho MR, Geraldeli S, Tay F, de Goes MF, Carvalho RM, Tjäderhane L, Reis AF, Hebling J, Mazzoni A, Breschi L, Pashley D (2007) In vivo preservation of the hybrid layer by chlorhexidine. J Dent Res 86:529–533

    Article  CAS  Google Scholar 

  35. De Munck J, Van den Steen PE, Mine A, Van Landuyt, KL, Poitevin A, Opdenakker G, Van Meerbeek B (2009) Inhibition of enzymatic degradation of adhesive-dentin interfaces. J Dent Res 88:1101–1106

    Article  Google Scholar 

  36. Kato, MT, Leite AL, Hannas AR, Calabria MP, Magalhães AC, Pereira JC, Buzalaf MA (2012) Impact of protease inhibitors in dentin matrix degradation by collagenase. J Dent Res 91:1119–1123

    Article  CAS  Google Scholar 

  37. Rai B, Kaur J, Jain R, Anand SC (2010) Levels of gingival crevicular metalloproteinases-8 and -9 in periodontitis. Saudi Dent J 2:129–131

    Article  Google Scholar 

  38. El-Sharkawy H, Aboelsaad N, Eliwa M, Darweesh M, Alshahat M, Kantarci A, Hasturk H, Van Dyke TE (2010) Adjunctive treatment of chronic periodontitis with daily dietary supplementation with omega-3 fatty acids and low-dose aspirin. J Periodontol 81:1635–1643

    Article  CAS  Google Scholar 

  39. Choi JS, Park NH, Hwang SY, Sohn JH, Kwak I, Cho KK, Choi IS (2013) The antibacterial activity of various saturated and unsaturated fatty acids against several oral pathogens. Environ Biol 34:673–676

    Google Scholar 

  40. Deore GD, Gurav AN, Patil R, Shete AR, Naiktari RS, Inamdar SP (2014) Omega 3 fatty acids as a host modulator in chronic periodontitis patients: a randomised, double-blind, palcebo-controlled, clinical trial. J Periodontal Implant Sci 44:25–32

    Article  CAS  Google Scholar 

  41. Sima C, Van Dyke TE (2016) Therapeutic targets for management of periodontitis and diabetes. Curr Pharm Des 22:2216–2237

    Article  CAS  Google Scholar 

  42. Chee B, Park B, Fitzsimmons T, Coates AM, Bartold PM (2016) Omega-3 fatty acids as an adjunct for periodontal therapy-a review. Clin Oral Investig 20:879–894

    Article  CAS  Google Scholar 

  43. Berton A, Rigot V, Huet E, Decarme M, Eeckhout Y, Patthy L, Godeau G, Hornebeck W, Bellon G, Emonard H (2001) Involvement of fibronectin type II repeats in the efficient inhibition of gelatinases A and B by long-chain unsaturated fatty acids. J Biol Chem 276:20458–20465

    Article  CAS  Google Scholar 

  44. Bieth JG (1995) Theoretical and practical aspects of proteinase inhibition kinetics. Methods Enzymol 248:59–84

    Article  CAS  Google Scholar 

  45. Fischer ER, Hansen BT, Nair V, Hoyt FH, Dorward DW (2012) Scanning Electron Microscopy. Curr Protoc Microbiol. Chapter 2:Unit 2B.2. doi:10.1002/9780471729259.mc02bs25

    Google Scholar 

  46. Goldberg M, Kulkarni AB, Young M, Boskey A (2011) Dentin: structure, composition and mineralization. Front Biosci 3:711–735

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Cristina Piro.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical Approval

Teeth were extracted after obtaining patients’ informed consent, as part of an overall treatment plan (University of Rome ‘Tor Vergata’ ethical committee approval, No. 129/16).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nicolai, E., Sinibaldi, F., Sannino, G. et al. Omega-3 and Omega-6 Fatty Acids Act as Inhibitors of the Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity. Protein J 36, 278–285 (2017). https://doi.org/10.1007/s10930-017-9727-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10930-017-9727-9

Keywords

Navigation