The role of extracellular ATP-mediated purinergic signaling in bone, cartilage, and tooth tissue

Background: Adenosine 5'-triphosphate (ATP) is a nucleotide that is known to play a multitude of important roles in intracellular energy metabolism in eukaryotic cells. It has also been reported that ATP acts as an extracellular autocrine and/or paracrine signaling molecule upon being secreted from a cell, affecting numerous downstream factors and signaling cascades involved in both normal cellular physiology and disease development. Highlight: Signaling that involves a purine nucleotide or nucleoside, such as ATP or other adenosine containing molecules (e.g., ADP, AMP, and adenosine), is called purinergic signaling. ATP-sensitive purinergic receptors include the P2Y family of G protein-coupled receptors and the P2X family of ligand- gated cation channels. These receptors have been characterized in almost all cell types. The vast amount of literature concerning these receptors has provided evidence that connects purinergic signaling with a variety of cellular functions. In this review, we summarize previous reports focused on extracellular ATP- mediated purinergic signaling observed in cells found in bone, cartilage, and teeth. Conclusion: Purinergic signaling is involved in osteogenesis, chondrogenesis, and dental sensory perception, indicating that ATP is an essential signaling molecule in bone, cartilage, and teeth. The downstream effects of ATP-mediated signaling are largely dependent on the receptors expressed in the tissue as well as the stage of cellular differentiation. While the current literature has greatly advanced our understanding of purinergic signaling, additional research is necessary to fully elucidate the function of ATP-mediated pathways.