Inflammation, Pain, and Pressure—Purinergic Signaling in Oral Tissues

Abstract

Signaling by extracellular purines such as ATP and adenosine has implications for dental research on multiple levels, with the association of purinergic signaling with inflammation, mechanical strain, and pain making the system particularly relevant for the specific challenges in the oral cavity. Oral tissues express a variety of G-protein-coupled P2Y receptors for ATP and P1 receptors for adenosine in addition to ionotropic P2X receptors for ATP. When these receptors are combined with the plethora of extracellular enzymes capable of manipulating extracellular agonist levels, a complex system for regulating oral health emerges, and recent findings have begun to identify a key role for purinergic signaling in oral pathophysiology. For example, the manipulation of extracellular ATP levels by P. gingivalis reduces inflammasome activation and apoptosis linked to P2X 7 receptor activation. Release of ATP by periodontal ligaments may link mechanical strain to bone remodeling. Activation of P2X receptors is implicated in dental pain, and receptor antagonists represent important targets for new analgesics. Altered levels of adenosine receptors in periodontal disease also suggest a role for nucleosides in dental signaling. The intricacies of the purinergic signaling system make it well-suited for the unique concerns of dental research, and future findings will doubtless confirm this importance.

A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection

“…P2X7 is an ion-gated channel that can participate in apoptotic cell death, and its ligand, extracellular adenosine triphosphate (eATP), is a prototypic DAMP, being implicated in IL-1β cleavage and secretion from proinflammatory cells (Pelegrin et al 2008). A large body of evidence indicates that stimulation by eATP, adenosine, and related compounds can affect many additional facets of oral pathophysiology, as recently reviewed (Lim and Mitchell 2012). Yilmaz et al (2008) showed that P. gingivalis stimulates synthesis of pro-IL-1β, but this first signal is not able to activate the NLRP3 inflammasome in gingival epithelial cells; however, addition of an exogenous source of ATP promoted secretion of the mature IL-1β.…”

Bone Morphogenetic Protein-9 Induces PDLSCs Osteogenic Differentiation through the ERK and p38 Signal Pathways

“…It causes progressive irreversible damage that leads to tooth loss 1. There is a link between periodontitis and systemic diseases such as diabetes and cardiovascular disease, which seriously impact patients' quality of life 2.…”

Th17 i IL-17 osiągają wyższe stężenia w przebiegu martwicy głowy kości udowej i są dodatnio skorelowane z nasileniem bólu

“…Inflammatory factors, such as tumour necrosis factor alpha (TNF-a) [9], nitric oxide (NO) [10], interleukin (IL)-33 [11], and several adhesion molecules [8], also participated in the pathogenesis of synovitis. Interestingly, these inflammatory cells and cytokines were reported to be involved in pain severity [12][13][14].…”