REVIEW ARTICLE Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc Sarit Sara Sivan • Anthony J. Hayes • Ellen Wachtel • Bruce Caterson • Yulia Merkher • Alice Maroudas • Sharon Brown • Sally Roberts Received: 12 December 2012 / Revised: 1 March 2013 / Accepted: 30 March 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract Background The intervertebral disc (IVD) is a complex cartilaginous structure which functions to resist biome- chanical loads during spinal movement. It consists of the highly viscous cartilaginous nucleus pulposus, which is surrounded laterally by a thick outer ring of fibrous carti- lage—the annulus fibrosus—and sandwiched inferiorly and superiorly by the cartilage end-plates. The main extracel- lular matrix molecules of the disc are collagens, proteo- glycans, glycoproteins and elastin. The disc also contains appreciable amounts of water, matrix-degrading protease enzymes and their inhibitors, soluble signalling molecules and various metabolic breakdown products. Methods This review provides a comprehensive descrip- tion of the biochemical composition of the extracellular matrix of the IVD and, specifically, the proteases involved in its molecular turnover. Quantitation of the turnover rates using racemization of aspartic acid as a molecular clock is also discussed. Conclusions Molecular turnover rates of the major con- stituent matrix macromolecules of the IVD are found to be particularly slow, especially in the case of collagen. Over a normal human life span, this slow turnover may compro- mise the structural integrity of the IVD extracellular matrix essential for normal physiological functioning. Keywords Intervertebral disc Á Turnover of extracellular matrix Á Collagen Á Elastin Á Proteoglycans Á Matrix metalloproteinases Á Aspartic acid racemization Introduction The intervertebral disc (IVD) has a heterogeneous structure with three distinct regions: the central nucleus pulposus (NP), the outer annulus fibrosus (AF) and the cartilage endplate (CEP). The biochemical heterogeneity of the mature IVD reflects its developmental origins and meta- bolic history that is shaped by diverse mechanical influ- ences experienced during growth and differentiation. Distinct populations of cells in each region that derive initially from the notochord and sclerotome during foetal development give rise to the NP and the AF, respectively [1]. These secrete and organise an extracellular matrix whose molecular composition plays a central role in the normal functioning of the IVD. The major biochemical constituents of the extracellular matrix in mature IVD tis- sue (i.e. collagen, proteoglycans, elastin and glycoproteins) are similar to those found in other musculoskeletal con- nective tissues (e.g. tendon, ligament and cartilage). In contrast to other connective tissues, however, they are commonly found in a particularly fragmented form [2]. Because healthy IVD tissue is avascular, these partially degraded fragments accumulate, with amounts increasing as a function of the age and state of degeneration of the disc. This paper describes the biochemical composition of the disc, measurement of the turnover of some constituent S. S. Sivan (&) Á Y. Merkher Á A. Maroudas Department of Biomedical Engineering, Technion, Israel Institute of Technology, 32000 Haifa, Israel e-mail: sivan.sarit@gmail.com A. J. Hayes Á B. Caterson School of Biosciences, Cardiff University, Cardiff, Wales, UK E. Wachtel Faculty of Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel S. Brown Á S. Roberts Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust and ISTM, Keele University, Oswestry, Shropshire SY10 7AG, UK 123 Eur Spine J DOI 10.1007/s00586-013-2767-8