CROBM CROBM & JDR Merger
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Golub, L. M.
Right arrow Articles by Rifkin, B. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Golub, L. M.
Right arrow Articles by Rifkin, B. R.

Critical Reviews in Oral Biology & Medicine, Vol 2, 297-321, Copyright © 1991 by International & American Associations for Dental Research

ARTICLES

Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs

L. M. Golub, N. S. Ramamurthy, T. F. McNamara, R. A. Greenwald and B. R. Rifkin
Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York, Stony Brook.

Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption. The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)-binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property. Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but still retain anti-collagenase activity. The first of these CMTs, 4-de-di-methylaminotetracycline, was found not to produce a major side-effect of antimicrobial tetracycline therapy--its administration to experimental animals did not result in the emergence of tetracycline-resistant microorganisms in the oral flora and gut. Numerous examples of the clinical potential of this non-antimicrobial property of tetracyclines in the treatment of periodontal and several medical diseases (e.g., sterile corneal ulcers, rheumatoid arthritis, skin bullous lesions, tumor-induced angiogenesis and metastasis) are discussed.


This article has been cited by other articles:


Home page
 Br. J. Ophthalmol.Home page
V A Smith, D Khan-Lim, L Anderson, S D Cook, and A D Dick
Does orally administered doxycycline reach the tear film?
Br. J. Ophthalmol., June 1, 2008; 92(6): 856 - 859.
[Abstract] [Full Text] [PDF]

Home page
 Am J Sports MedHome page
S. P. Arnoczky, M. Lavagnino, M. Egerbacher, O. Caballero, and K. Gardner
Matrix Metalloproteinase Inhibitors Prevent a Decrease in the Mechanical Properties of Stress-Deprived Tendons: An In Vitro Experimental Study
Am. J. Sports Med., May 1, 2007; 35(5): 763 - 769.
[Abstract] [Full Text] [PDF]

Home page
 J ANIM SCIHome page
J. R. E. del Castillo, V. Laroute, P. Pommier, C. Zemirline, A. Keita, D. Concordet, and P.-L. Toutain
Interindividual variability in plasma concentrations after systemic exposure of swine to dietary doxycycline supplied with and without paracetamol: A population pharmacokinetic approach
J Anim Sci, November 1, 2006; 84(11): 3155 - 3166.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
H. Levkovitch-Verbin, M. Kalev-Landoy, Z. Habot-Wilner, and S. Melamed
Minocycline delays death of retinal ganglion cells in experimental glaucoma and after optic nerve transection.
Arch Ophthalmol, April 1, 2006; 124(4): 520 - 526.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
B. J. Dezube, S. E. Krown, J. Y. Lee, K. S. Bauer, and D. M. Aboulafia
Randomized Phase II Trial of Matrix Metalloproteinase Inhibitor COL-3 in AIDS-Related Kaposi's Sarcoma: An AIDS Malignancy Consortium Study
J. Clin. Oncol., March 20, 2006; 24(9): 1389 - 1394.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. S. Kocer, S. G. Walker, B. Zerler, L. M. Golub, and S. R. Simon
Metalloproteinase Inhibitors, Nonantimicrobial Chemically Modified Tetracyclines, and Ilomastat Block Bacillus anthracis Lethal Factor Activity in Viable Cells
Infect. Immun., November 1, 2005; 73(11): 7548 - 7557.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Kaliski, L. Maggiorella, K. A. Cengel, D. Mathe, V. Rouffiac, P. Opolon, N. Lassau, J. Bourhis, and E. Deutsch
Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion
Mol. Cancer Ther., November 1, 2005; 4(11): 1717 - 1728.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
T. J. Kaitu'u, J. Shen, J. Zhang, N. B. Morison, and L. A. Salamonsen
Matrix Metalloproteinases in Endometrial Breakdown and Repair: Functional Significance in a Mouse Model
Biol Reprod, October 1, 2005; 73(4): 672 - 680.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Syed, C. Takimoto, M. Hidalgo, J. Rizzo, J. G. Kuhn, L. A. Hammond, G. Schwartz, A. Tolcher, A. Patnaik, S. G. Eckhardt, et al.
A Phase I and Pharmacokinetic Study of Col-3 (Metastat), an Oral Tetracycline Derivative with Potent Matrix Metalloproteinase and Antitumor Properties
Clin. Cancer Res., October 1, 2004; 10(19): 6512 - 6521.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. S. Yao, Y. Chen, W. Zhai, K. Xu, W. L. Young, and G.-Y. Yang
Minocycline Exerts Multiple Inhibitory Effects on Vascular Endothelial Growth Factor-Induced Smooth Muscle Cell Migration: The Role of ERK1/2, PI3K, and Matrix Metalloproteinases
Circ. Res., August 20, 2004; 95(4): 364 - 371.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
T. Krakauer and M. Buckley
Doxycycline Is Anti-Inflammatory and Inhibits Staphylococcal Exotoxin-Induced Cytokines and Chemokines
Antimicrob. Agents Chemother., November 1, 2003; 47(11): 3630 - 3633.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. Q. Li, T. Y. Shang, H.-S. Kim, A. Solomon, B. L. Lokeshwar, and S. C. Pflugfelder
Regulated Expression of Collagenases MMP-1, -8, and -13 and Stromelysins MMP-3, -10, and -11 by Human Corneal Epithelial Cells
Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2928 - 2936.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
W. Briest, A. Holzl, B. Rassler, A. Deten, H. A Baba, and H.-G. Zimmer
Significance of matrix metalloproteinases in norepinephrine-induced remodelling of rat hearts
Cardiovasc Res, February 1, 2003; 57(2): 379 - 387.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
R. E. B. Seftor, E. A. Seftor, D. A. Kirschmann, and M. J. C. Hendrix
Targeting the Tumor Microenvironment with Chemically Modified Tetracyclines: Inhibition of Laminin 5 {gamma}2 Chain Promigratory Fragments and Vasculogenic Mimicry
Mol. Cancer Ther., November 1, 2002; 1(13): 1173 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
Y. Liu, M. E. Ryan, H.-M. Lee, S. Simon, G. Tortora, C. Lauzon, M. K. Leung, and L. M. Golub
A Chemically Modified Tetracycline (CMT-3) Is a New Antifungal Agent
Antimicrob. Agents Chemother., May 1, 2002; 46(5): 1447 - 1454.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. C. M. Duivenvoorden, S. V. Popovic, S. Lhotak, E. Seidlitz, H. W. Hirte, R. G. Tozer, and G. Singh
Doxycycline Decreases Tumor Burden in a Bone Metastasis Model of Human Breast Cancer
Cancer Res., March 1, 2002; 62(6): 1588 - 1591.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Cianfrocca, T. P. Cooley, J. Y. Lee, M. A. Rudek, D. T. Scadden, L. Ratner, J. M. Pluda, W. D. Figg, S. E. Krown, and B. J. Dezube
Matrix Metalloproteinase Inhibitor COL-3 in the Treatment of AIDS-Related Kaposi's Sarcoma: A Phase I AIDS Malignancy Consortium Study
J. Clin. Oncol., January 1, 2002; 20(1): 153 - 159.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
T. Imamura, K. Matsushita, J. Travis, and J. Potempa
Inhibition of Trypsin-Like Cysteine Proteinases (Gingipains) from Porphyromonas gingivalis by Tetracycline and Its Analogues
Antimicrob. Agents Chemother., October 1, 2001; 45(10): 2871 - 2876.
[Abstract] [Full Text]

Home page
 Int ImmunolHome page
I. I. Kuzin, J. E. Snyder, G. D. Ugine, D. Wu, S. Lee, T. Bushnell Jr, R. A. Insel, F. M. Young, and A. Bottaro
Tetracyclines inhibit activated B cell function
Int. Immunol., July 1, 2001; 13(7): 921 - 931.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. A. Rudek, W. D. Figg, V. Dyer, W. Dahut, M. L. Turner, S. M. Steinberg, D. J. Liewehr, D. R. Kohler, J. M. Pluda, and E. Reed
Phase I Clinical Trial of Oral COL-3, a Matrix Metalloproteinase Inhibitor, in Patients With Refractory Metastatic Cancer
J. Clin. Oncol., January 15, 2001; 19(2): 584 - 592.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. Vieillard-Baron, E. Frisdal, S. Eddahibi, I. Deprez, A. H. Baker, A. C. Newby, P. Berger, M. Levame, B. Raffestin, S. Adnot, et al.
Inhibition of Matrix Metalloproteinases by Lung TIMP-1 Gene Transfer or Doxycycline Aggravates Pulmonary Hypertension in Rats
Circ. Res., September 1, 2000; 87(5): 418 - 425.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. Sobrin, Z. Liu, D. C. Monroy, A. Solomon, M. G. Selzer, B. L. Lokeshwar, and S. C. Pflugfelder
Regulation of MMP-9 Activity in Human Tear Fluid and Corneal Epithelial Culture Supernatant
Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1703 - 1709.
[Abstract] [Full Text]

Home page
 Antimicrob. Agents Chemother.Home page
D. Grenier, M.-P. Huot, and D. Mayrand
Iron-Chelating Activity of Tetracyclines and Its Impact on the Susceptibility of Actinobacillus actinomycetemcomitans to These Antibiotics
Antimicrob. Agents Chemother., March 1, 2000; 44(3): 763 - 766.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
R. N. Patel, M. G. Attur, M. N. Dave, I. V. Patel, S. A. Stuchin, S. B. Abramson, and A. R. Amin
A Novel Mechanism of Action of Chemically Modified Tetracyclines: Inhibition of COX-2-Mediated Prostaglandin E2 Production
J. Immunol., September 15, 1999; 163(6): 3459 - 3467.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. G. Attur, R. N. Patel, P. D. Patel, S. B. Abramson, and A. R. Amin
Tetracycline Up-Regulates COX-2 Expression and Prostaglandin E2 Production Independent of Its Effect on Nitric Oxide
J. Immunol., March 15, 1999; 162(6): 3160 - 3167.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Yrjanheikki, R. Keinanen, M. Pellikka, T. Hokfelt, and J. Koistinaho
Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia
PNAS, December 22, 1998; 95(26): 15769 - 15774.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. R. Amin, M. G. Attur, G. D. Thakker, P. D. Patel, P. R. Vyas, R. N. Patel, I. R. Patel, and S. B. Abramson
A novel mechanism of action of tetracyclines: Effects on nitric oxide synthases
PNAS, November 26, 1996; 93(24): 14014 - 14019.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. R. Davies, A. A. Cole, and T. M. Schmid
Doxycycline Inhibits Type X Collagen Synthesis in Avian Hypertrophic Chondrocyte Cultures
J. Biol. Chem., October 18, 1996; 271(42): 25966 - 25970.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
IADR Journals Advances in Dental Research ®
Journal of Dental Research ® Critical Reviews (1990-2004)
Copyright © 1991 Institutional Access Guidelines