The role of disc cell heterogeneity in determining disc biochemistry: a speculation.

The nucleus pulposus is a key player in very early disc degeneration. In the young disc, by acting as a water-like fluid, as opposed to a solid, it resists compression and instantaneously distributes forces evenly in all directions to the inner annulus. The disc anlage notochordal cells contribute not only to how the disc develops, but also to the matrix of the young disc at a time when the nucleus is at its most fluid-like. In humans, the notochordal cells disappear early, when there is a transformation of the nucleus into a more solid cartilaginous tissue. In cell culture, the co-cultures of the notochordal cells and chondrocytic cells enhance proteoglycan synthesis by the opposite cell type due, at least partly, to soluble factors. The continued presence of notochordal cells in vivo may provide protection. In work by others, in vivo reinsertion of notochordal-rich nucleus pulposus in a damaged disc will delay annular degeneration. The notochordal cells in the nucleus may have a different phenotype from when they are in the notochord and they may go through a changing programme of expression critical to disc development and maintaining a fluid-like nucleus. Little is known about why, in many species, the notochordal cells die early during growth and only the chondrocytic cells persist. This area offers an interesting avenue of research that may lead to very early intervention in disc degeneration.