Degradation of basement membranes and stromal extracellular matrix (ECM) is crucial for invasion and metastasis of malignant cells. Degradation of ECM is initiated by proteinases secreted by different cell types participating in tumor cell invasion, and increased expression or activity of every known class of proteinases (metallo-, serine-, aspartic-, and cysteine) has been linked to malignancy and invasion of tumor cells. Studies performed over the last decade have revealed that matrix metalloproteinases (MMPs) play a crucial role in tumor invasion. Expression of MMP genes is transcriptionally regulated by a variety of extracellular factors including cytokines, growth factors, and cell contact to ECM. This review will summarize the current view on the role of MMPs in tumor growth, invasion, and survival, and focus on the role of mitogen-activated protein kinases and AP-1 and ETS transcription factors in the regulation of MMP gene expression during invasion process.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fasebj.13.8.781

Regulation of matrix metalloproteinase expression in tumor invasion

The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth. The susceptibility to periodontitis appears to be determined by the host response; specifically, the magnitude of the inflammatory response and the differential activation of immune pathways. The purpose of this review was to delineate our current knowledge of the host response in periodontitis. The role of innate immunity, the failure of acute inflammation to resolve (thus becoming chronic), the cytokine pathways that regulate the activation of acquired immunity and the cells and products of the immune system are considered. New information relating to regulation of both inflammation and the immune response will be reviewed in the context of susceptibility to, and perhaps control of, periodontitis.

/pdf/inflammatory-and-immune-pathways-in-the-pathogenesis-of-4igej65lbb.pdf

Inflammatory and immune pathways in the pathogenesis of periodontal disease.

Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.

http://www.site2012.sbd-sp.org.br/public/img/destaques/destaque26.pdf

Tetracyclines: Nonantibiotic properties and their clinical implications

Matrix metalloproteinases (MMPs) form a family of enzymes that mediate multiple functions both in the tissue destruction and immune responses related to periodontal inflammation. The expression and activity of MMPs in non-inflamed periodontium is low but is drastically enhanced to pathologically elevated levels due to the dental plaque and infection-induced periodontal inflammation. Soft and hard tissue destruction during periodontitis and peri-implantitis are thought to reflect a cascade of events involving bacterial virulence factors/enzymes, pro-inflammatory cytokines, reactive oxygen species and MMPs. However, recent studies suggest that MMPs can also exert anti-inflammatory effects in defence of the host by processing anti-inflammatory cytokines and chemokines, as well as by regulating apoptotic and immune responses. MMP-inhibitor (MMPI)-drugs, such as doxycycline, can be used as adjunctive medication to augment both the scaling and root planing-treatment of periodontitis locally and to reduce inflammation systematically. Furthermore, MMPs present in oral fluids (gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), mouth-rinses and saliva) can be utilized to develop new non-invasive, chair/bed-side, point-of-care diagnostics for periodontitis and dental peri-implantitis.

https://www.tandfonline.com/doi/pdf/10.1080/07853890600800103

Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation.

Matrix metalloproteinases (MMPs) are a group of enzymes that in concert are responsible for the degradation of most extracellular matrix proteins during organogenesis, growth and normal tissue turnover. The expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction, such as inflammatory diseases, tumour growth and metastasis. MMPs have a marked role also in tissue destructive oral diseases. The role of collagenases, especially MMP-8, in periodontitis and peri-implantitis is the best-known example of the unwanted tissue destruction related to increased presence and activity of MMPs at the site of disease, but evidence has been brought forward to indicate that MMPs may be involved also in other oral diseases, such as dental caries and oral cancer. This brief review describes some of the history, the current status and the future aspects of the work mainly of our research groups looking at the presence and activity of various MMPs in different oral diseases, as well as some of the MMP-related aspects that may facilitate the development of new means of diagnosis and treatment of oral diseases.

Matrix metalloproteinases (MMPs) in oral diseases.

Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells - Regulation by tumor necrosis factor-alpha and doxycycline

Tiina Kainulainen

Papers

Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells - Regulation by tumor necrosis factor-alpha and doxycycline