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 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 1  |  Issue : 2  |  Page : 65-69

Role of matrix metalloproteinases (MMPS) in periodontitis and its management


Department of Periodontics, K.S.R Institute of Dental Sciences and Research, K. S. R. Kalvi Nagar, Tiruchengode, Namakkal District, Tamil Nadu, India

Date of Web Publication31-Dec-2014

Correspondence Address:
Dr. Esther Nalini Honibald
Professor, Department of Periodontics, K. S. R. Institute of Dental Sciences and Research, K. S. R. Kalvi Nagar, Tiruchengode - 637215, Namakkal District, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2229-3019.148262

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  Abstract 

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that mediate the degradation of extracellular matrix (ECM) macromolecules. The activity of MMPs is seen not only during normal organogenesis and wound healing, but also in pathological condition like inflammatory diseases. MMP synthesis and functions are regulated by transcriptional activation, post-transcriptional processing and by a family of endogenous inhibitors collectively known as tissue inhibitors of metalloproteinases (TIMPs). The balance of MMPs to TIMPs therefore determines matrix turnover, where either an excess of MMPs or a deficit of TIMPs may result in excess ECM degradation. This review describes the role of MMPs in periodontitis and its management.

Keywords: Matrix metalloproteinases, tissue inhibitors of metalloproteinases, extracellular matrix, chemically modified tetracyclines, low-dose doxycycline, chronic periodontitis


How to cite this article:
Charles K, Honibald EN, Reddy N R, Palani A, Ramamurthy RD, Sankaralingam T. Role of matrix metalloproteinases (MMPS) in periodontitis and its management. J Indian Acad Dent Spec Res 2014;1:65-9

How to cite this URL:
Charles K, Honibald EN, Reddy N R, Palani A, Ramamurthy RD, Sankaralingam T. Role of matrix metalloproteinases (MMPS) in periodontitis and its management. J Indian Acad Dent Spec Res [serial online] 2014 [cited 2019 Mar 18];1:65-9. Available from: http://www.jiadsr.org/text.asp?2014/1/2/65/148262


  Introduction Top


Extracellular matrix (ECM) macromolecules play a key role in development and morphogenesis. Matrix metalloproteinases (MMPs), also called matrixins, are an important family of metal-dependent endopeptidases responsible for the degradation of ECM components. Expression of the 28 matrixins genes in humans is transcriptionally controlled by inflammatorycytokines, growth factors, hormones, and cell-cell and cell-matrix interactions. Matrixin activities are also regulated by activation of the precursor zymogens and inhibition by endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Thus, the balance between MMPs and TIMPs are critical for the eventual ECM remodeling.

The MMP family

The following are the MMPs grouped according to their substrate specificity. [1]

Collagenases

MMP-1 (collagenase-1, interstitial collagenase), MMP-8 (collagenase-2, neutrophil collagenase), and MMP-13 (collagenase-3).

Gelatinases

MMP-2 (gelatinase A, 72kDa gelatinase), MMP-9 (gelatinase B, 92kDa gelatinase).

Stromelysins

MMP-3 (stromelysin-1), MMP-10 (stromelysin-2), MMP-11 (stromelysin-3), and MMP-12 (metalloelastase).

Matrilysins

MMP-7 (matrilysin, PUMP-1) and MMP-26 (matrilysin-2).

MT-MMPs (membrane type)

MMP-14 (MT1-MMP), MMP-15 (MT2-MMP), MMP-16 (MT3-MMP), MMP-17 (MT4-MMP), MMP-24 (MT5-MMP), and MMP-25 (MT6-MMP).

Other MMPs

MMP-18, MMP-19, MMP-20 (enamelysin), MMP-21, MMP-23, MMP-27, and MMP-28 (epilysin).

Regulation of MMP activity

The activity of MMP against ECM substrates is regulated at four "gates": [2]

  1. Transcriptional regulation of MMP genes;
    1. Growth factors and cytokines-like interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-alpha and beta, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (B-FGF) induce MMPs
    2. Hormonal regulation
    3. Cell shape and cell substrate adhesion
    4. Second messenger signaling.
  2. Precursor activation;
  3. Differences in substrate specificity; and
  4. MMP inhibitors.


Alpha 2-macroglobulins

Active MMP are captured by alpha 2-macroglobulins by a unique venus-fly-trap mechanism activated by cleavage of a bond in the "bait region". This cleavage leads to hydrolysis of a labile internal thiol-ester bond and covalent cross-linking of a nascent glutamyl residue to lysyl side chains exposed on the surface of the attacking proteinase. [2]

TIMPs

The first TIMP was described in 1975 as a protein, in culture medium of human fibroblasts and in human serum, which was able to inhibit collagenase activity. The molecular weight of this protein was later shown to be 28.5 kDa. Since then, three new TIMPs have been discovered in different species, and have been designated TIMP-2, -3, and -4, respectively. [3]

Role of MMPS in periodontal diseases

In periodontal diseases, MMPs play key roles in the degradation of the ECM, basement membrane and protective serpins as well as in the modification of cytokine action and activation of osteoclasts. Both resident gingival and periodontal ligament fibroblasts produce collagenases that are thought to be involved in normal tissue turnover. Inflammatory cells such as neutrophils and macrophages produce MMPs, with neutrophils being the major source of collagenase and gelatinase in inflammatory diseases such as periodontitis. Epithelial cells can also produce elevated levels of these enzymes, which may facilitate the apical migration and lateral extension of the junctional epithelium and the subsequent loss of connective tissue attachment. Inflammatory cells, particularly neutrophils, are thought to play a particularly important role in the MMP-mediated periodontal destructive lesion. [4]

Osteoblasts express fibroblast collagenase (FIB-CL) when stimulated by bone-resorbing agents. Osteoclastic bone resorption is initiated by an osteoblast response to resorptive signals such as parathyroid hormone (PTH), which includes expression of FIB-CL and perhaps other MMPs, and result in dissolution of the unmineralized collagenous osteoid layer [Table 1]. [4]
Table 1: Role of matrix metalloproteinases (MMPs) in periodontal diseases

Click here to view


Exogenous (Synthetic) MMP inhibitors

Inhibiting MMPs can be an effective adjunctive treatment in the management of periodontitis as they are important mediators in the connective tissue breakdown in periodontitis.

Inhibitors of MMPs fall into three pharmacologic categories: [20]

  1. Collagen peptidomimetics and nonpeptidomimetics,
    1. Peptidomimetic MMP inhibitors
    2. Batimastat
    3. Marimastat
    4. Nonpeptidic MMP inhibitors
    5. BAY 12-9566
    6. AG3340
    7. BMS-27529
    8. CGS-27023A
  2. Tetracycline derivatives,
    1. Doxycycline
    2. Col-3 (metastat)
  3. Bisphosphonates.
    1. In [Table 2] and [Table 3] related studies of exogenous inhibitors has been discussed
      Table 2: MMP inhibitors: In vitro studies

      Click here to view
      Table 3: MMP inhibitors: Clinical studies

      Click here to view



  Conclusion Top


MMPs are important components in many biological and pathological processes because of their ability to degrade ECM components. ECM and basement membrane destruction are key events in the initiation and progression of periodontal disease. These processes involve the cooperative activities and cascades of both host and bacterial derived proteolytic enzymes. The role of MMPs in the destructive processes of periodontal disease has been proved, distinguishing them as a viable target for a chemotherapeutic approach. The use of MMP inhibitor as an adjunct to conventional periodontal treatment can enhance and make clinical therapeutic responses more predictable. [29]

 
  References Top

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29.
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    Tables

  [Table 1], [Table 2], [Table 3]


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