The extracellular matrix of the intervertebral disc structures contains
many molecules also found in cartilage. The extremely polyanionic
proteoglycans play a central role, particularly in the nucleus, by creating an
osmotic environment leading to retention of water and ensuing resistance to
deformation—important for the resilience of the tissue.
Another major structural entity particularly important in the anulus is the
network of collagen fibers; fibril-forming collagen 1 is a major constituent.
The collagen fibrils in the anulus are largely oriented in sheets around the
nucleus. A number of molecules present in the matrix regulate and direct the
collagen fibril assembly by interacting with the collagen molecule and also
the formed fibril. Several of these molecules bind by one domain to the
collagen fiber and present another functional domain to interact either with
other fibers or with other matrix constituents. In this manner the collagen
fibers are cross-linked into a network that provides tensile strength and
distributes load over large parts of the anulus. Diminished function in these
cross-bridging molecules will lead to loss of mechanical properties of the
collagen network and result in an impaired ability of the anulus to resist
forces delivered by compression of the disc and particularly the nucleus.
A different network abundant in the disc and in other load-bearing tissues
is based on the beaded filaments of collagen 6. The basic building block is a
tetramer of two pairs of antiparallel collagen-6 molecules arranged such that
two N-terminal ends of collagen 6 are exposed at either end of the unit.
Further assembly occurs both by end-to-end and side-to-side associations. This
process is catalyzed by both biglycan and decorin, where the combined effect
of direct binding of the core protein to the collagen-6 N-terminal globular
domain and the presence of the glycosaminoglycan side chain is essential.
These ligands are bound at the same site in complexes extracted from the
tissue and then also have one bound molecule of matrilin-1, 2, or 3, in turn
bound to a collagen fiber, a procollagen molecule, or an aggrecan.
Interactions at the cell surface provide signals to the cells with regard
to the conditions of the matrix. Such interactions include binding by matrix
components to various receptors at the cell surface.
Remodeling of the matrix takes place in response to various factors. An
early event in disease is degradation of aggrecan by the members of the ADAMTS
(a disintegrin-like and metalloprotease with thrombospondin motifs) family and
degradation of molecules important in maintaining the collagen network.