Increased Expression in Nucleus Pulposus Cells in Response to High Oxygen


Goal of the Study?

In this qualitative primary research study from the Oxidative Medicine and Cellular Longevity Journal 1 the authors’ goal was to determine the potential role of the Integrin Alpha 6 receptor in the inner nucleus pulposus in response to high oxygen tension in intervertebral disc degeneration.


Why are they doing this study?

Intervertebral Disc Degeneration (IVDD) is the most common musculoskeletal disorder and a major cause of disability.  The development of IVDD is directly associated with several factors including ageing, genetic susceptibility, body weight, heavy workload and smoking.  The Intervertebral Disc (IVD) mainly consists of three tissue compartments; the outer Annulus Fibrosus (AF), the inner Nucleus Pulposus (NP) and the cephalic and caudal cartilage endplates.  The AF and NP tissues work together to provide two major anatomical functions of the IVD; spinal flexibility and load distribution.  Increasing evidence suggests that integrins such as Alpha 6 (⍺6) are involved in the pathogenesis of IVDD, however, the exact method by which the low oxygen environment initiates IVDD is not fully understood.


What was done?

Twenty-five MRI scans of surgical patients were categorized using the Pfirrmann classification system.  Degenerated specimens were obtained from 21 patients who underwent spinal fusion surgery with low back pain.  Normal disc specimens were taken from four young patients with burst lumbar fracture without IVDD.  Eighteen research rats were euthanized and the Co4-5 caudal discs were collected and analyzed.  Both human and rat specimens were analyzed by a series of histology stainings.  The NP cells were isolated and cultured.  A complex sequence of procedures and analyses were performed.  These were designed to explore the relationship between the ⍺6 integrins and the oxygen content of the NP tissue.


What did they find?

The study demonstrated for the first time that the expression of the integrin ⍺6 increased significantly in the IVDD at an early degeneration stage.  The increase of oxygen content of the NP tissue was a critical factor for the upregulation of this ⍺6 integrin.  Furthermore silencing this integrin in vivo appears to accelerate puncture-induced IVDD.   As such this study concludes that the increase of the ⍺6 integrin is a critical protective factor in IVD degeneration as well as acting to restore the NP cell function.


Why do these findings matter?

Low back pain due to IVDD affects many individuals, especially in the elderly population and identifying the mechanisms of IVDD and finding new therapeutic targets is critical.  This study confirmed that the expression of integrin ⍺6 was increased during the early stages of disc degeneration.  It also confirmed that the destruction of the hypoxia environment in the NP tissue is a leading cause of the increased ⍺6  integrin.  It is hoped that this study provides a foundation for new insights into the development of pharmacological and physical therapies that can modify the course of IVDD.


Dynamic Disc Designs create realistically crafted disc models to help in the education of back pain and degenerative disc disease. This important paper revealed how oxygen infiltration into the nucleus pulposus upregulates integrin ⍺6 as protective against IVDD.

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