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Identifying a New Treatment for Periodontitis

Human Fibroblasts: Important Cells in Wound Healing and Inflammation

Fibroblasts are the most common cell type comprising the connective tissue in humans and other mammals. These spindle-shaped cells synthesize extracellular matrix proteins that provide the structural framework, or stroma, for animal tissues. Besides their well-known structural role, fibroblasts are important in the wound healing response to tissue injury, as well as initiating inflammation in the presence of invading microorganisms.

Specifically, gingival fibroblasts, the most abundant structural cell in periodontal (gum) connective tissue, play a key role in the maintenance and repair of periodontal tissues as well as in inflammatory periodontal diseases. Lifeline’s human gingival fibroblasts (HGFs) have been used extensively in studies involving periodontal tissues. In a previous blog, they were used for cytotoxicity testing of dental cement compositions. A new publication, to be discussed below, utilizes these fibroblasts to study the development and treatment of periodontitis.

For information on HGFs and other Lifeline® fibroblasts, please check out our catalog:

Recent Research Using Lifeline Gingival Fibroblasts

Periodontitis is a chronic inflammatory gum disease caused by gram-negative bacterial infections that can arise due to poor oral hygiene. Bacteria and plaque buildup around the tooth elicit an inflammatory immune response that can damage the soft tissue and bone supporting the tooth. Left untreated, periodontitis can result in tooth loss and jaw damage.

Human gingival fibroblasts (HGFs) are known to play a key role in the development of periodontal disease through their interactions with the infection-causing bacteria.  Additionally, high levels of matrix metalloproteinase (MMP) appear to be a significant risk factor for the progression of periodontal disease. In HGFs, stimulation of cytokine interleukin (IL)-1β induced the expression of MMP-3 and inflammatory cytokines such as IL-6 and IL-8, which are responsible for osteoclast activation and differentiation, results in soft tissue loss and alveolar bone (the part of the jaw that holds the teeth) destruction.

Previous research identified reversine, a 2,6-disubstituted purine derivative, as having an inhibitory effect on MMP and inflammatory cytokine expression. Therefore, in this publication, Song and colleagues sought to not only determine the underlying mechanism driving reversine inhibition of IL-lβ-stimulated cytokine and MMP-3 expression in Lifeline’s HGFs, but to evaluate it as a potential therapeutic for periodontal disease.

Utilizing real-time quantitative PCR, the investigators determined that reversine inhibited MMP-3, IL-6 and IL-8 expression in HGFs stimulated with IL-1β. The cellular responses induced by IL-1β are mediated by different intracellular signaling cascades, including map kinase (MAPK)/AP-1 and IκB kinase (IKK)/NF-κB in HGFs. Therefore, the researchers focused on these pathways to elucidate the underlying mechanism of reversine inhibition. In these studies, they discovered reversine inhibited the phosphorylation of several MAPKs as determine by Western blot. Furthermore, reversine interfered with IL-1β-induced activation of transcription factors NF-κB and AP-1 by inhibiting translocation of p-c-Jun and prevented DNA binding.

Reactive oxygen species (ROS) produced by immune cells like neutrophils and eosinophils are involved in inflammatory responses to infection.  High levels of ROS can cause cellular damage and tissue destruction in periodontal disease. Reversine inhibited IL-1β-induced ROS production as determined by DCF-DA fluorescence.

Taken together, Song and colleagues determined that reversine significantly inhibits IL-1β-induced MMP-3, IL-6, and IL-8 expression by downregulating MAPK/AP-1 activation and ROS generation. The data from this study provides strong evidence that reversine is effective and suitable as a therapeutic to prevent periodontal disease.

If you’ve used Lifeline products in your research, we’d love to hear from you. Your study could be featured next time here on the blog!

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