Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 2, March-April, p. 383–390

doi: 10.17219/acem/30428

Publication type: review article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The Significance of Matrix Metalloproteinases in Oral Diseases

Mateusz Maciejczyk1,A,B,C,D,F, Agnieszka Pietrzykowska1,A,B,C,D,F, Anna Zalewska2,A,B,E,F, Małgorzata Knaś3,A,B,F, Irena Daniszewska4,A,B

1 Students’ Scientific Group “Stomatological Biochemistry”, Department of Conservative Dentistry, Medical University of Bialystok, Poland

2 Department of Conservative Dentistry, Medical University of Bialystok, Poland

3 Institute of Health Care, Higher Vocational School, Suwałki, Poland

4 Specialist Dental Practice, Białystok, Poland


Matrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known to play a key role in the catabolic turnover of extracellular matrix (ECM) components. Research studies to date have indicated that MMPs regulate the activity of several non-ECM bioactive substrates, including growth factors, cytokines, chemokines and cell receptors, which determine the tissue microenvironment. Disruption of the balance between the concentration of active matalloproteinases and their inhibitors (TIMPs) may lead to pathological changes associated with uncontrolled ECM turnover, tissue remodeling, inflammatory response, cell growth and migration. This brief review presents some information on MMPs’ role in inflammatory, metabolic and cancer abnormalities related to the salivary glands, as well as MMP-related aspects that lead to the formation of human dentinal caries lesions. In oral diseases, the most relevant biological fluid commonly used for diagnosing periodontal diseases is saliva. In diseased patients with significantly higher levels of MMPs in their saliva than healthy people, most extracellular matrix components undergo digestion to lower molecular weight forms. Conventional treatment successfully reduces the levels of MMPs inhibits the progressive breakdown of gingival and periodontal ligament collagens. Beside inflammatory abnormalities like Sjögren’s syndrome (SS), a large group of disorders is comprised of cancers, most of them involving the parotid gland.

Key words

dental caries, matrix metalloproteinases, tissue inhibitors of metalloproteinases, salivary glands, oral diseases

References (48)

  1. Roy R, Yan GJ, Moses MA: Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 2009, 27, 5287–5297.
  2. Shiomi T1, Lemaître V, D’Armiento J, Okada Y: Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int 2010, 60, 477–496.
  3. Raffetto JD1, Khalil RA: Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 2008, 75, 346–359.
  4. Kessenbrock K, Plaks V, Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010, 141, 52–67.
  5. Sela-Passwell N, Rosenblum G, Shoham T, Sagi I: Structural and functional bases for allosteric control of MMP activities: can it pave the path for selective inhibition? Biochim Biophys Acta 2010, 1803, 29–38.
  6. Manicone MA, McGuire JK: Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol 2008, 19, 34–41.
  7. Nan H, Niu T, Hunter DJ, Han J: Missense Polymorphisms in Matrix Metalloproteinase Genes and Skin Cancer Risk. Cancer Epidemiol Biomarkers Prev 2008, 17, 3551–3557.
  8. Gialeli C, Theocharis AD, Karamanos NK: Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 2011, 278, 16–27.
  9. Herszényi L, Hritz I, Lakatos G, Varga MZ, Tulassay Z: The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci 2012, 13, 13240–13263.
  10. Chen Q, Jin M, Yang F Zhu J, Xiao Q, Zhang L: Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling. Mediators Inflamm 2013, Article ID 928315, 14 pages. http://
  11. Benjamin MM, Khalil RA: Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease. EXS 2012, 103, 209–279.
  12. Tallant C, Marrero A, Gomis-Rüth FX: Matrix metalloproteinases: Fold and function of their catalytic domains. Biochim Biophys Acta 2010, 1803, 20–28.
  13. Van Hinsbergh VW, Koolwijk P: Endothelial sprouting and angiogenesis: Matrix metalloproteinases in the lead. Cardiovasc Res 2008, 78, 203–212.
  14. Jackson BC, Nebert DW, Vasiliou V: Update of human and mouse matrix metalloproteinase families. Hum Genomics 2010, 4, 194–201.
  15. Edwards DR, Handsley MM, Pennington CJ: The ADAM metalloproteinases. Mol Aspects Med 2008, 29, 258–289.
  16. Etique N, Verzeaux L, Dedieu S, Emonard H: LRP-1: A checkpoint for the extracellular matrix proteolysis. BioMed Res Int 2013, Article ID 152163, 7 pages.
  17. Gingras D, Béliveau R: Emerging concepts in the regulation of membrane-type 1 matrix metalloproteinase activity. Biochim Biophys Acta 2010, 1803, 142–150.
  18. Kerkelä E, Saarialho-Kere U: Matrix metalloproteinases in tumor progression: Focus on basal and squamous cell skin cancer. Exp Dermatol 2003, 12, 109–125.
  19. Schlöndorff J, Blobel CP: Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 1999, 112 (Pt 21), 3603–3617.
  20. Tocchi A, Parks WC: Functional interactions between matrix metalloproteinases and glycosaminoglycans. FEBS J 2013, 280, 2332–2341.
  21. Sternlicht MD, Werb Z: How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 2001, 17, 463–516.
  22. Strongin AY: Proteolytic and non-proteolytic roles of membrane type-1 matrix metalloproteinase in malignancy. Biochim Biophys Acta 2010, 1803, 133–141.
  23. Yan C, Boyd DD: Regulation of matrix metalloproteinase gene expression. J Cell Physiol 2007, 211, 19–26.
  24. Lenglet S, Mach F, Montecucco F: Role of matrix metalloproteinase-8 in atherosclerosis. Mediators Inflamm 2013, 2013, 659282.
  25. Folgueras AR, Pendás AM, Sánchez LM, López-Otín C: Matrix metalloproteinases in cancer: From new functions to improved inhibition strategies. Int J Dev Biol 2004, 48, 411–424.
  26. Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA, Kang JD: Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J 2013, 13, 331–341.
  27. Dziankowska-Bartkowiak B, Waszczykowska A, Żebrowska A: The role of metalloproteinases and their inhibitors in the pathomechanism of skin diseases. Alerg Astma Immunol 2004, 9, 71–79.
  28. Hadler-Olsen E, Fadnes B, Sylte I: Regulation of matrix metalloproteinase activity in health and disease. FEBS J 2011, 278, 28–45.
  29. Philips N, Auler S, Hugo R, Gonzalez S: Beneficial regulation of matrix metalloproteinases for skin health. Enzyme Res 2011, 427285.
  30. Brew K, Nagase H: The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity. Biochim Biophys Acta 2010, 1803, 55–71.
  31. Stetler-Stevenson WG: Tissue inhibitors of metalloproteinases in cell signaling: Metalloproteinase-independent biological activities. Sci Signal 2008, 1, re6. DOI: 10.1126/scisignal.127re6.
  32. Cruz-Munoz W, Khokha R: The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci 2008, 45, 291–338.
  33. Murphy G: Tissue inhibitors of metalloproteinases. Genome Biol 2011, 12, 233.
  34. Cheng XC, Fang H, Xu WF: Advances in assays of matrix metalloproteinases (MMPs) and their inhibitors. J Enzyme Inhib Med Chem 2008, 23, 154–167.
  35. Patil PB, Patil BR: Saliva: A diagnostic biomarker of periodontal diseases. J Indian Soc Periodontol 2011, 15, 310–317.
  36. Malamud D: Saliva as a diagnostic fluid. Dent Clin North Am 2011, 55, 159–178.
  37. Sodek J, Overall CM: Matrix metalloproteinases in periodontal tissue remodelling. Matrix Suppl 1992, 1, 352–362.
  38. Mäkelä M, Salo T, Uitto VJ: Matrix metalloproteinases (MMP-2 and MMP-9) of the oral cavity: Cellular origin and relationship to periodontal status. J Dent Res 1994, 73, 1397–1406.
  39. Costa PP, Trevisan GL, Macedo GO: Salivary interleukin-6, matrix metalloproteinase-8, and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol 2010, 81, 384–391.
  40. Amano O, Mizobe K, Bando Y: Anatomy and Histology of Rodent and Human Major Salivary Glands. Acta Histochem Cytochem 2012, 45, 241–250.
  41. Reina S, Passafaro D, Sterin-Borda L: Atorvastatin inhibits the inflammatory response caused by anti-M(3) peptide IgG in patients with primary Sjögren’s syndrome. Inflammopharmacology 2012, 20, 267–275.
  42. Tincani A, Andreoli L, Cavazzana I, Doria A, Favero M, Fenini MG, Franceschini F, Lojacono A, Nascimbeni G, Santoro A, Semeraro F, Toniati P, Shoenfeld Y: Novel aspects of Sjögren’s syndrome in 2012. BMC Med 2013, 11, 93.
  43. Molina C, Alliende C, Aguilera S: Basal lamina disorganisation of the acini and ducts of labial salivary glands from patients with Sjögren’s syndrome: Association with mononuclear cell infiltration. Ann Rheum Dis 2006, 65, 178–183.
  44. Wildenberg ME, van Helden-Meeuwsen CG, Drexhage HA: Altered fractalkine cleavage potentially promotes local inflammation in NOD salivary gland. Arthritis Res Ther 2008, 10, R6 9.
  45. Whitt JC, Schafer DR, Callihan MD: Multiple malignant salivary gland neoplasms: Mucoepidermoid carcinoma of palate and adenoid cystic carcinoma of floor of mouth. Head Neck Pathol 2008, 2, 41–48.
  46. Deryugina EI, Quigley JP: Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: Contrasting, overlapping and compensatory functions. Biochim Biophys Acta 2010, 1803, 103–120.
  47. Sorsa T, Tjäderhane L, Salo T: Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 2004, 10, 311–318.
  48. Shimada Y, Ichinose S, Sadr A, Burrow MF, Tagami J: Localization of matrix metalloproteinases (MMPs-2, 8, 9 and 20) in normal and carious dentine. Aust Dent J 2009, 54, 347–354.