In situ oxygen utilization in the rat intervertebral disc
Year: 2007
Type: article
Abstract: Nucleus pulposus cells of the intervertebral disc have no endogenous vasculature and have thus been hypothesized to be hypoxic. This hypothesis was tested using 2-nitroimidazole, EF5, a drug that at low oxygen concentrations forms covalent adducts with cellular proteins. After administrating EF5 to rats, sections of the intervertebral disc were analysed for EF5 adducts. Drug adducts were quantified in tissue sections using a fluorescent monoclonal antibody. Although the level of EF5 fluorescence in all intervertebral disc tissues was low, the transition zone at the periphery of the nucleus pulposus exhibited the highest level of EF5 binding. To substantiate this result, tissue nitroreductase levels and drug pharmacology were evaluated. Nitroreductase levels were measured in whole discs under severe hypoxia. We noted that there was robust EF5 binding to cells in the annulus fibrosus and transition zone with modest binding to cells of the nucleus pulposus and endplate. High-performance liquid chromatography analysis indicated limitations in EF5 access to the nucleus pulposus, most probably related to the lack of vasculature and slow drug distribution through the gel-like interior of the disc. However, despite diffusion problems, the drug dose was determined to be sufficient to report the oxygen status of the nucleus pulposus cells. Based on these findings, we conclude that despite poor vascularization, the disc cells accommodate to the local environment by displaying a limited need for oxygen. Accordingly, the cells of the intervertebral disc are not severely hypoxic.
Source: Journal of Anatomy
Institutions: Thomas Jefferson University, University of Pennsylvania
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Smart Substrates for a New Generation of Implants, G15147311, BONE GROWTH IN DENTAL, CRANIAL AND SKELETAL TISSUES, G1909204376, Predicting Radiation Response by Tumor pO2, G4059859911, G4314844868, CRANIOFACIAL DEVELOPMENT: METABOLIC CONTROL OF APOPTOSIS, G5858734587, REGULATION OF APOPTOSIS IN OSTEOBLAST-LIKE CELLS
OpenAlex ID: W2042226041