TRIGEMINAL AFFERENTS REGULATION OF APICAL PERIODONTITIS DEVELOPMENT

Apical periodontitis (AP) is a highly prevalent and debilitating pathological condition marked bybone resorption and pain as result of dental infections. Many elegant studies have revealed thefunctions of immune cells and inflammatory mediators in AP. Despite AP being denselyinnervated by trigeminal ganglia (TG) fibers, the participation of these afferents in this diseaseprocess is largely unknown. Our preliminary data demonstrate that TG neurons regulate APlesion development. The objective of this proposal is to understand how TG fibers control APdevelopment, which remains a large gap in knowledge. We, for the first time, propose toinvestigate neurons/non-neuronal cell interaction in control of AP development for each of fourmajor subclasses of TG neurons. This is novel and critically important strategy in approachingresearch on regulation of AP development by sensory neurons, since each neuronal sub-classhas distinct function and biochemical make up, including unique sets of receptors, ion channelsand neuropeptides. Hence, it is possible that regulatory potential of TG neuronal subsets coulddramatically vary; and even produce opposite effects on osteoclasts and osteoblasts. Soaccording to literature and preliminary experiments, we designed a novel strategy on study APdevelopment by TG neurons. Our central hypothesis is that in response to infection certainsubclasses of TG afferents inhibit bone resorption in apical periodontitis via the regulation ofosteoclastic and osteoblastic activities. This hypothesis will be tested in: Aim 1 examining roleof different subclasses of TG afferents in inhibiting bone resorption and immunologicalresponses in a murine model of infection-induced AP; Aim 2 defining involvement of differentsubclasses of TG neurons on regulation of osteoclastic and osteoblastic functions; and Aim 3defining and identifying the released soluble factor(s) from different subclasses of TG neuronsand their contribution to modulation of osteoclast and osteoblast functions. We believe thatknowledge generated by this application will have a substantial positive impact from bothscientific and clinical perspectives. Scientifically, this is the principally novel approach ininvestigation of AP using subclass-specific TG mouse lines. Moreover, the generated newinsight into interactions between neurons and DCS remodeling will open pathways for furtherscientific advancement. Clinically, identification of neuronal regulatory mechanisms could offernovel strategies and, importantly, targets for developing anti-AP therapeutics.