Abstract
As the most common cause of low back pain, the cascade of intervertebral disc (IVD) degeneration is initiated by the disappearance of notochordal cells and progressive loss of proteoglycan (PG). Limited nutrient supply in the avascular disc environment restricts the production of ATP which is an essential energy source for cell survival and function such as PG biosynthesis. The objective of this study was to examine ATP level and PG production of porcine IVD cells under prolonged exposure to hypoxia with physiological glucose concentrations. The results showed notochordal NP and AF cells responded differently to changes of oxygen and glucose. Metabolic activities (including PG production) of IVD cells are restricted under the in-vivo nutrient conditions while NP notochordal cells are likely to be more vulnerable to reduced nutrition supply. Moreover, provision of energy, together or not with genetic regulation, may govern PG production in the IVD under restricted nutrient supply. Therefore, maintaining essential levels of nutrients may reduce the loss of notochordal cells and PG in the IVD. This study provides a new insight into the metabolism of IVD cells under nutrient deprivation and the information for developing treatment strategies for disc degeneration.
Highlights
As a leading cause of global disability, low back pain (LBP) creates a significant social economic burden[1]
High cell viability of both nucleus pulposus (NP) and annulus fibrosus (AF) cells were observed after tissue digestion (Figs. 1, 2a,b) and after seeding in agarose constructs(Fig. 2c,d)
We investigated intracellular ATP content, PG production, cell viability, glucose consumption rate and gene expression of facilitative glucose transporters and aggrecan of intervertebral disc (IVD) cells cultured in a sequential reduction of glucose under both normoxia and hypoxia for 6 days
Summary
As a leading cause of global disability, low back pain (LBP) creates a significant social economic burden[1]. Cells rely on nutrient supply for survival and function Since key nutrients such as glucose and oxygen can only be delivered to cells by diffusion through the dense ECM from capillaries at the endplate or the margins of AF due to the avascular nature of the IVD15–17, ECM transport properties and cellular consumption establish sharp concentration gradients of nutrients with lowest values at the disc center (i.e., NP region)[18,19,20], which imposes challenges to maintain a healthy cell condition within the IVD. The energy metabolism of IVD cells under glucose deprivation and hypoxia and its association with disc degeneration have not been elucidated.
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