Analysis of Extracellular ATP Distribution in the Intervertebral Disc

Abstract

Progressive loss of proteoglycans (PGs) is the major biochemical change during intervertebral disc (IVD) degeneration. Adenosine triphosphate (ATP) as the primary energy source is not only critical for cell survival but also serves as a building block in PG synthesis. Extracellular ATP can mediate a variety of physiological functions and was shown to promote extracellular matrix (ECM) production in the IVD. Therefore, the objective of this study was to develop a 3D finite element model to predict extracellular ATP distribution in the IVD and evaluate the impact of degeneration on extracellular ATP distribution. A novel 3D finite element model of the IVD was developed by incorporating experimental measurements of ATP metabolism and ATP-PG binding kinetics into the mechano-electrochemical mixture theory. The new model was validated by experimental data of porcine IVD, and then used to analyze the extracellular distribution of ATP in human IVDs. Extracellular ATP was shown to bind specifically with PGs in IVD ECM. It was found that annulus fibrosus cells hydrolyze ATP faster than that of nucleus pulposus (NP) cells whereas NP cells exhibited a higher ATP release. The distribution of extracellular ATP in a porcine model was consistent with experimental data in our previous study. The predictions from a human IVD model showed a high accumulation of extracellular ATP in the NP region, whereas the extracellular ATP level was reduced with tissue degeneration. This study provides an understanding of extracellular ATP metabolism and its potential biological influences on the IVD via purinergic signaling.

Keywords: ATP binding; Degeneration; Extracellular ATP; Finite element model; Intervertebral disc; Proteoglycan.