Dichotomy of Phosphate Actions in Periodontal Health

About This Grant

Phosphate (PO43-/Pi) is a natural component of animal and plant food sources and is widely used as food additive in the modern Western diet. With the high consumption of processed foods, the average dietary Pi intake greatly exceeds the body requirements and recommended dietary allowance in the United States. The pathological consequences of the dietary Pi overload include inflammation and disrupted bone metabolism. On the other hand, Pi insufficiency, either systemic or at the cellular level, results in impaired formation of skeletal and dental tissues. Pi is a signaling molecule that changes cellular physiology. This function of Pi depends on levels of available Pi, but outcomes depend on a type of a cell exposed to Pi, that is on its molecular makeup and transcriptional program. In vitro studies from our and other labs implicate GATA-type transcription factors in regulation of gene expression in response to Pi. We have shown that Trps1 (a GATA-type transcription factor) is critical for recognizing and responding to available Pi in cells producing mineralized extracellular matrix. Importantly, our published and preliminary data also revealed that Pi regulates the activity of this transcription factor suggesting that Pi and Trps1 form a regulatory loop controlling gene expression in skeletal and dental tissues. The goal of the proposed study is to determine the interplay between dietary Pi availability, its pro-osteogenic and pro-inflammatory effects and the Trps1-regulated formation and homeostasis of the periodontium. Periodontium is a multi-tissue structure that anchors the tooth to the jaw bone and provides a barrier protecting the underlying tissues from the oral microbiota. At least two of the periodontal tissues (cementum and bone) depend on adequate Pi availability, which is highlighted by increased susceptibility and severity of periodontal disease in individuals with Pi deficiency. Periodontal disease is a highly prevalent inflammatory condition affecting at least 2 in 5 adults aged 45−64 years in the United States. Our preliminary data from Trps1Col1a1 cKO mice detected periodontal defects characteristic for Pi deficiency, further supporting the involvement of Trps1 in cellular responses to Pi. Hence, we hypothesize that the interplay between the Pi availability and Trps1-regulated bone and cementum development maintains the homeostasis of periodontium. We will address this hypothesis through a set of in vivo experiments that will: 1) determine the effects of dietary Pi intake on Trps1 activity in osteoblasts and cementoblasts; 2) define the relationship between the dietary Pi intake and the Trps1-dependent formation of the cementum and alveolar bone; 3) determine the consequences of the dietary Pi overload on sound and genetically compromised periodontium in the context of disrupted periodontal homeostasis. Results of these studies will provide the understanding of the differences between healthy and impaired alveolar bone responses to Pi availability and inflammatory challenge, which will facilitate development of preventive and therapeutic strategies aimed at improving periodontal health in individuals with genetically impaired periodontal structure.