Intervertebral Disc Proteoglycans: Multifunctional Tissue Stabilizing and Instructional Cell Regulatory Proteins That Control Tissue Homeostasis

The intervertebral disc (IVD) is a tough fibrocartilaginous viscoelastic cushion interposed between spinal vertebrae. It has a composite structure whose material properties are due to the interplay between fibrillar collagens which, provide high tensile strength and hydrodynamic IVD proteoglycans (PGs) such as aggrecan that provide weight-bearing properties. Other PGs such as the small leucine-rich PGs, have roles in collagenous assembly and organization and interactions with growth factors and cytokines. Elastin in the annular lamellae provides resilient properties to tissues. A total of 19 IVD PGs have been identified; three recently identified PGs, perlecan, bikunin and lubricin have particularly interesting properties that affect tissue function. Perlecan is a multifunctional HSPG that provides tissue stabilization and promotes cellular proliferation and differentiation during spinal development, IVD repair and cell-extracellular matrix communication as well as osmoregulatory properties allowing the disc cell to sense and respond to its biomechanical microenvironment to maintain tissue function and regulate IVD homeostasis. Bikunin, the light chain of inter-α-trypsin inhibitor (ITI) has tissue protective properties and roles in the transfer of the heavy chains of ITI to hyaluronan which, aids in its stabilization. Lubricin is a boundary lubricant identified in the surface regions of articular cartilage but its roles in the IVD have yet to be fully determined. It may aid in the lubrication of collagen fiber bundles in the annulus fibrosus allowing them to slide over each other during torsional loading. Emerging roles for lubricin in cell regulation and control of inflammation may also be relevant to IVD regulatory processes. This review illustrates the diverse structure and function of IVD PGs and their roles in cellular regulation and tissue function. Fragmentation of IVD PGs during normal tissue turnover generates some interesting bioactive PG fragments of potential application in tissue repair and regenerative processes that warrant further investigation.