The International Journal of Biochemistry & Cell Biology 40 (2008) 837–842 Available online at www.sciencedirect.com Medicine in focus Pathophysiology of the human intervertebral disc Alessandra Colombini a,1 , Giovanni Lombardi a,b,1 , Massimiliano Marco Corsi c,d , Giuseppe Banfi a,e,∗ a Laboratory of Cell Culture and Molecular Biology, IRCCS, Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milan, Italy b Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Via F.lli Cervi 93, 20090 Segrate, Milan, Italy c Laboratory of Biotechnological Applications, IRCCS, Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milan, Italy d Institute of General Pathology, Lab of Clinical Pathology, University of Milan, Via L. Mangiagalli 31, 20133 Milan, Italy e Dipartimento di Tecnologie per la Salute, School of Medicine, University of Milan, Via R. Galeazzi 4, 20161 Milan, Italy Received 25 October 2007; received in revised form 20 December 2007; accepted 20 December 2007 Available online 28 December 2007 Abstract Intervertebral disc degeneration is a common invalidating disorder that can affect the musculoskeletal apparatus in both younger and older ages. The chief component of the intervertebral disc is the highly organized extracellular matrix; maintenance of its organization is essential for correct spinal mechanics. The matrix components, mainly proteoglycans and collagens, undergo a slow and continuous cell-mediated turnover process that enables disc cells to adapt their environment to external stimuli. Cellular senescence and a history of chronic abnormal loading can upset this balance, leading to progressive tissue failure that results in disc degeneration. Although biological treatment approaches to disc repair are still far to come, advances in our understanding of disc biochemistry and in defining the role of genetic inheritance have provided a starting point for developing new concepts in the diagnosis, therapy and prevention of disc degeneration. © 2008 Elsevier Ltd. All rights reserved. Keywords: Intervertebral disc degeneration; Proteoglycans; Collagens; Extracellular matrix turnover Abbreviations: ECM, extracellular matrix; IVD, intervertebral disc; NP, nucleus pulposus; AF, annulus fibrosus; AGE, advanced gly- cation end product; CS, chondroitin sulphate; KS, keratan sulphate; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metallo- proteinase; VNTR, variable number of tandem repeats; SNP, single nucleotide polymorphism. ∗ Corresponding author at: Laboratory of Cell Culture and Molecu- lar Biology, IRCCS, Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milan, Italy. Tel.: +39 0266214827; fax: +39 0266214806. E-mail address: giuseppe.banfi1@unimi.it (G. Banfi). 1 These authors contributed equally to this work. 1. Introduction About 25% of the height of the human spine is occu- pied by the 23 intervertebral discs (IVDs) that articulate and anchor the vertebral bodies together, act either as shock absorbers and load transmitting units from body weight and muscle activity through the spinal column. The disc is a heterogeneous structure; its functional prop- erties strikingly depend on the composition, organization and integrity of the extracellular matrix (ECM) produced and maintained by a few resident cells. Alterations in cel- 1357-2725/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biocel.2007.12.011