Accumulation of Extracellular ATP in Porcine Nucleus Pulposus

There are many reasons for people to miss work; one of the leading contributors is low back pain (LBP), which is believed to affect 80% of the population at some point during their lifetime. Suffering from back pain is the chief complaint of 5% of people who visit the doctor in the US [1]. The total medical cost related to low back pain in the US exceeds 100 billion dollars every year [2]. The cause of LBP is still unclear. However, recent studies revealed that intervertebral disc (IVD) degeneration is closely related to LBP [3]. IVD transfers loads and allows the spine to move through torsion, bending or compression [4–6]. There are two main anatomic regions in IVD: nucleus pulposus (NP) and annulus fibrosis (AF). The loss of notochordal cells in the NP region has been associated with the initiation of disc degeneration [7]. Our recent studies demonstrated that the adenosine triphosphate (ATP) production of notochordal NP cells was much higher than that of the AF cells while mechanical loading promoted ATP release from IVD cells [8]. Extracellular ATP (eATP) is a powerful signaling molecule that can mediate a wide variety of biological responses, such as cell metabolism, survival, and growth by binding to the purinergic receptors: G protein coupled receptor (P2Y) or ligand-gated ionotropic receptor (P2X) [9]. In addition, eATP is often rapidly hydrolyzed by several families of ectonucleotidases [10–12]. The by-products of eATP hydrolysis include inorganic pyrophosphate (PPi) and phosphate (Pi) which are closely related to mineral crystal formation and tissue calcification [12–15]. PPi and Pi released from eATP hydrolysis may contribute to endplate calcification which has been associated with disc degeneration. However, eATP accumulation in the IVD has not been studied yet. Therefore, the objective of this study was to investigate the accumulative level of eATP in the NP region of porcine IVD using a novel optical ATP sensor.