Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors

Bone ◽  
2004 ◽  
Vol 35 (2) ◽  
pp. 471-478 ◽  
Author(s):  
S.G Holmes ◽  
K Still ◽  
D.J Buttle ◽  
N.J Bishop ◽  
P.S Grabowski
Keyword(s):  
Chemically Modified ◽  
Osteoclast Precursors ◽  
Chemically Modified Tetracyclines

Bullet for periodontal disease in future: Chemically modified tetracyclines

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.

Role of Chemically Modified Tetracyclines in the Management of Periodontal Diseases: A Review

Drug Research ◽  
2017 ◽  
Vol 67 (05) ◽  
pp. 258-265 ◽  
Author(s):  
Archit Ghangurde ◽  
Kiran Ganji ◽  
Manohar Bhongade ◽  
Bhumika Sehdev
Keyword(s):  
Animal Studies ◽  
Metabolic Diseases ◽  
Periodontal Diseases ◽  
Gelatinase Activity ◽  
Chemically Modified ◽  
Periodontal Breakdown ◽  
Osteoclast Function ◽  
Chemically Modified Tetracyclines

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.

Inhibition of MMP Synthesis by Doxycycline and Chemically Modified Tetracyclines (CMTs) in Human Endothelial Cells

1998 ◽  
Vol 12 (1) ◽  
pp. 114-118 ◽  
Author(s):  
R. Hanemaaijer ◽  
H. Visser ◽  
P. Koolwijk ◽  
T. Sorsa ◽  
T. Salo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Western Blotting ◽  
Broad Spectrum ◽  
Mrna Level ◽  
Gelatin Zymography ◽  
Human Endothelial Cells ◽  
Broad Spectrum Antibiotic ◽  
Chemically Modified ◽  
Specific Regulation ◽  
Chemically Modified Tetracyclines

Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs in human endothelial cells. Doxycycline (50 μM) completely inhibited the phorbol-12-myristate-13-acetate (PMA)-mediated induction of MMP-8 and MMP-9, as measured by Western blotting and gelatin zymography, respectively. The inhibition was also observed at the mRNA level. No effect was observed on the expression of MMP-2 and of the MMP inhibitors TIMP-1 and TIMP-2. Chemically modified tetracyclines (CMTs) showed an inhibition similar to that of doxycycline, albeit less efficient. These observations demonstrate that endothelial cells display a specific regulation of MMPs, which may have implications for the pharmaceutical interaction in angiogenesis and angiogenesis-related diseases.

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