ROLE OF CHEMICALLY MODIFIED TETRACYCLINES ON HEPATIC MATRIX METALOPROTEINASES IN SEPSIS.

AbstractResearchers have found that Chemically Modified Tetracyclines (CMTs) act through multiple mechanisms, affecting several parameters of osteoclast function and consequently inhibit bone resorption by altering intracellular calcium concentration and interacting with the putative calcium receptor; decreasing ruffled border area; diminishing acid production; diminishing the secretion of lysosomal cysteine proteinases (cathepsins); inducing cell retraction by affecting podosomes; inhibiting osteoclast gelatinase activity; selectively inhibiting osteoclast ontogeny or development; and inducing apoptosis or programmed cell death of osteoclasts. Thus TCs/CMTs, as anti-resorptive drugs, may act similarly to bisphosphonates and primarily affect osteoclast function. Researchers have evaluated the influence of various chemically modified tetracyclines from CMT-1 to CMT-10 on collagenases and gelatinases through in vitro or animal studies and concluded that all the CMTs except CMT-5 inhibited periodontal breakdown through MMP inhibition in the following order of efficacy: CMT-8>CMT-1>CMT-3>CMT-4>CMT-7. Thus the non-antimicrobial actions of the chemically modified analogues of tetracyclines have shown remarkably better mechanisms to those of agents with established anti-inflammatory/antioxidant potential. These findings clarify the multi-faceted actions of tetracyclines which are unique amongst antimicrobials, with therapeutic applications in periodontal and metabolic diseases. Hence, the present review describes the role of chemically modified tetracyclines in the management of periodontal diseases.

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Tetracycline-Based MMP Inhibitors Can Prevent Fibroblast-Mediated Collagen Gel Contraction In Vitro

Advances in Dental Research ◽

10.1177/08959374980120012701 ◽

1998 ◽

Vol 12 (1) ◽

pp. 86-93 ◽

Cited By ~ 22

Author(s):

S.A. Myers ◽

R.G. Wolowacz

Keyword(s):

Culture Media ◽

Collagen Gel ◽

Collagen Gels ◽

Cytotoxic Effects ◽

Chemically Modified ◽

Tissue Culture Media ◽

Collagen Gel Contraction ◽

Chemically Modified Tetracyclines

Collagen gels in vitro can be contracted by fibroblasts. The role of matrix metalloproteinases (MMPs) in the contraction of collagen lattices by human neonatal foreskin fibroblasts (HuFFs) was investigated in tissue culture media supplemented by various doses of known gelatinase inhibitors. Fluorescent assays with model gelatinase substrates and media conditioned by fibroblasts apparently confirmed the ability of chemically modified tetracyclines (CMTs) to act as inhibitors of MMP2, and zymography demonstrated that this was the major cell-derived MMP activity. There were no observable effects on the rate of contraction of attached FPCLs containing 6 x 104 HuFFs (passages 18-25) with either CMT-5 or CMT-2 at all concentrations tested (0-100 μg/mL). However, at greater than 20 μg/mL doxycycline and greater than 5 μg/mL CMT-3, FPCL contraction was completely abolished. Quantitative assessment of cell viability by means of the MTT assay in monolayer and qualitatively within the FPCLs with CalceinAM suggested that differences were not due to cytotoxic effects. Seeding FPCLs with lower-passage fibroblasts produced identical trends. These results may implicate the involvement of MMPs in the process of gel contraction, although tetracyclines have effects additional to their ability to inhibit MMPs directly.

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A Role for Non-Antimicrobial Actions of Tetracyclines in Combating Oxidative Stress in Periodontal and Metabolic Diseases: A Literature Review

The Open Dentistry Journal ◽

10.2174/1874210600802010005 ◽

2008 ◽

Vol 2 (1) ◽

pp. 5-12 ◽

Cited By ~ 34

Author(s):

M Soory

Keyword(s):

Oxidative Stress ◽

Metabolic Diseases ◽

Periodontal Diseases ◽

Mechanisms Of Action ◽

Matrix Synthesis ◽

Biological Targets ◽

Chemically Modified ◽

Chemically Modified Tetracyclines ◽

Inflammatory Burden

This review addresses the role of adjunctive tetracycline therapy in the management of periodontal diseases and its efficacy in reducing inflammatory burden, oxidative stress and its sequelae in patients with coexisting features of metabolic syndrome. Removal of the dimethylamine group at C4 of the tetracycline molecule reduces its antibiotic properties, enhancing its non-antimicrobial actions; this strategy has aided the development of several chemically modified tetracyclines such as minocycline and doxycycline, by altering different regions of the molecule for focused action on biological targets. Tetracyclines are effective in reducing inflammation by inhibiting matrix metalloproteinases, preventing excessive angiogenesis, inhibiting apoptosis and stimulating bone formation. There are important applications for tetracyclines in the management of diabetic, dyslipidaemic periodontal patients who smoke. The diverse mechanisms of action of tetracyclines in overcoming oxidative stress and enhancing matrix synthesis are discussed in this review.

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ROLE OF rhBMP-2 AND rhBMP-7 IN THE METABOLISM AND DIFFERENTIATION OF OSTEOBLAST-LIKE CELLS CULTURED ON CHEMICALLY MODIFIED TITANIUM SURFACES

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-12-00071.1 ◽

2012 ◽

pp. 141208072802005

Author(s):

Fabiano Ribeiro Cirano ◽

ADRIANE TOGASHI ◽

MARCIA MARQUES ◽

FRANCISCO PUSTIGLIONI ◽

LUIZ LIMA

Keyword(s):

Chemically Modified ◽

Titanium Surfaces ◽

Cells Cultured

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Bullet for periodontal disease in future: Chemically modified tetracyclines

Journal of Cellular Biotechnology ◽

10.3233/jcb-210040 ◽

2021 ◽

pp. 1-7

Author(s):

Shivani Sachdeva ◽

Ameet Mani ◽

Harish Saluja

Keyword(s):

Chronic Periodontitis ◽

Periodontal Ligament ◽

Host Response ◽

Alveolar Bone ◽

Gastrointestinal Toxicity ◽

Collagenolytic Activity ◽

Periodontal Pathogens ◽

Oral Biofilm ◽

Chemically Modified ◽

Chemically Modified Tetracyclines

Chronic periodontitis is nowadays popularly regarded as Dysbiosis, [1] which causes destruction of tissues rich in collagen like periodontal ligament, alveolar bone and gingival connective tissue. The oral biofilm comprises many periodontal pathogens better regarded as ‘triggers’ in causing chronic periodontitis. Since, not everyone will be affected in the same manner due to periodontal pathogens. Some might not elicit a host response while, the others might have exaggerated response. So, host modulation therapy came into existence to counteract the exaggerated host response. The chemically modified tetracyclines (CMTs) have emerged to inhibit the inflammatory response or to reduce the collagenolytic activity of host. Though a derivative of tetracyclines, it still lacks an antimicrobial action and hence, can be used for periodontitis for longer duration with no adverse effects of gastrointestinal toxicity which parent tetracyclines have.

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