The role of endplate calcification, nutritional vessel occlusion and proteins responsible for the elaboration of inorganic pyrophosphate in the pathogenesis of cervical disc degenerative disease

The origin, development and resultant effects of disc degenerative disease (DDD) have been investigated for decades, however the exact DDD pathogenesis remains unknown. The intervertebral disc (IVD) is the largest avascular (not supplied with blood vessels) structure in the human body. In lumbar IVDs some cells might be up to 8 mm away from the closest blood vessel. The IVD is separated from the vertebral bodies by caudal and cranial endplates – thin but firm layers of hyaline (glass-like) cartilage.

Grave damage, elusive culprit

Masson’s trichrome staining. From left to right, in a sagittal section: bone marrow of the vertebral body, endplate (dark blue), intervertebral disk (light blue). The red colour visible against the dark blue is the calcification of the endplate.

There are a myriad of factors predisposing to IVD degeneration – among them ageing, biochemical changes, impaired nutrient transport, genetic factors, mechanical overload and trauma. DDD influences the height of the IVD, thus changing spinal column, muscle and ligament biomechanics. In the long term DDD may lead to spinal canal stenosis (narrowing) – one of the main causes of pain and disability amongst the elderly. IVDs start to degenerate very early in the course of our life, faster than any other musculoskeletal tissues. Initial degenerative changes in lumbar IVDs can be noticed even in 11-16 year-olds. About 20% of all adolescents have mild IVD degeneration. This percentage changes rapidly, with 10% of 50 year-olds and 60% of 70 year-olds affected by advanced DDD.

One of the main causes thought to lead to DDD is the impairment of nutrient transport to the IVD. The fall in nutrient concentration in IVD cells leads to a drop in pH (due to increased concentration of lactates). This results in the reduced ability of IVD cells to synthesise and maintain the extracellular matrix, thus leading to degeneration.

I have chosen to work on the described subject because of a number of reasons. Firstly, the exact mechanisms leading to DDD are still shrouded in mystery. We possess only a vague idea about DDD pathogenesis and the role of endplate calcification (the accumulation of calcium salts in endplates), nutritional vessel occlusion (closure), the possible remodelling of capillaries and the expression of specific proteins responsible for the elaboration of inorganic pyrophosphate in the course of DDD. Secondly, we know that proteins responsible for the elaboration of inorganic pyrophosphate may cause cartilage calcification e.g. in growth plates in bones or cartilage surfaces of joints. However their influence on IVDs remains unknown. Thirdly, currently, there are no reports describing the microvascular architecture of the human endplate.

Proteins suspected

The author of this study assumes that the increased expression of specific proteins responsible for the elaboration of inorganic pyrophosphate causes IVD endplate calcification. During this process, the capillaries present in the endplate that supply the IVD with nutrients might undergo vascular remodelling. Alternatively, the lumen of these vessels might become partially or fully blocked due to a build-up of calcium deposits. This would lead to decreased nutrient transport to the IVD, and as a consequence, would cause DDD.

That is why the main aims of this study are to assess the role of proteins responsible for the elaboration of inorganic pyrophosphate in the process of cervical IVD endplate calcification, and to describe the microvascular architecture of the human endplate in patients with and without DDD.

Better preventive action against DDD?

The results of this project will allow us to better understand whether and how the expression of specific proteins responsible for the elaboration of inorganic pyrophosphate influences IVD endplate calcification. The author also plans to assess the changes occurring in the endplate’s microvascular architecture during its calcification. In case of positive results, the outcomes of this study will allow us to search in the future for new sites of action for drugs that may slow down the progression of DDD.

Krzysztof A. Tomaszewski MD

Graduated from the Jagiellonian University Medical College (Krakow) in 2011. He currently works as a teaching and research assistant in the Department of Anatomy JUMC and as a resident orthopaedic surgeon in the Department of Orthopaedics and Trauma Surgery (5^th Military Clinical Hospital, Krakow). He is an author or co-author of over 60 research manuscripts and 30 congress abstracts. His interests focus primarily on basic (anatomy, biomechanics, pathology, immunology and molecular biology) and clinical research (orthopaedics, orthopaedic oncology and sports medicine).

Masson’s trichrome staining. From left to right, in a sagittal section: bone marrow of the vertebral body, endplate (dark blue), intervertebral disk (light blue). The red colour visible against the dark blue is the calcification of the endplate.

Date of publication: 3^rd Jul, 2014