(v) Molecular and cellular biology of the intervertebral disc and the use of animal models

Abstract

Numerous in vivo animal models for intervertebral disc (IVD) research have been developed and now play an important role in promoting our understanding of normal disc biology, degeneration and potential therapeutic mechanisms. Heterogeneous cell types occur in the IVD, which have to adapt to an environment rather unique to the body in several senses, being exposed to severe hypoxia, high mechanic loading and hyperomostic pressure. IVD cells therefore must have specific mechanisms activated to adapt themselves to function in such harsh conditions. The most prominent change observed during IVD degeneration is the progressive loss of proteoglycan, water, and collagen II in the nucleus pulposus (NP) matrix. Most of these alterations can be attributed to cellular changes, including the decline in cell abundance and functionality and a shift of cells with chondrocytic phenotype to a fibrocytic phenotype. It is widely recognized that local environmental conditions within the degenerative disc, including nutrient supply, anabolic/catabolic factors, the responsiveness of functional cells and availability of supportive cells, and matrix scaffold, are factors that should be considered important when designing a therapeutic approach. Whereas future work will still require animal models to answer specific questions, their relevance to disc degeneration in patients with discogenic pain will now need to be carefully justified. © 2008 Elsevier Ltd. All rights reserved.