The intrevertebral disc is a unique joint responsible for the flexibility and cushioning properties of the vertebrate spine. Clinically, low back pain is one of the leading causes of work-related disability and over 80% of the population will at some time have back pain. The biology of the intervertebral disc is important to the understanding of spine biomechanics as well as processes such as aging, degeneration and mechanisms for pain production and its potential relief or prevention. The intervertebral disc, an avascular structure, consists of an annulus fibrosis and a nucleus pulposis, each containing specialized, highly organized collagen networks intermeshed with matrix glycoproteins and proteoglycans. This proposal deals with the characterization of the proteoglycan component with respect to the nature of the molecules present in the tissue as compared to those originally synthesized with special reference to the assembly and movement of aggregate structures through the matrix, the stochiometry of assembly and synthesis, their structure with respect to carbohydrate components and their potential maturation by a post-ribosomal modification. This work will be done in vivo using a rabbit model system and in vitro in both the rabbit and human system. The overall goal is to define the interactions between proteoglycans and other matrix components as related to the ability of cells to continue to express and preserve a functional matrix. This will include characterization of both human and rabbit nucleus and annulus proteoglycans using radioactive precursors for the carbohydrate and proteins, and hetero- and homofunctional crosslinking agents to map contact areas between link protein, hyaluronic acid and proteoglycan.
| Oegema Jr, T R; Swedenburg, S M; Bradford, D S et al. (1988) Levels of keratan sulfate-bearing fragments rise predictably following chemonucleolysis of dog intervertebral discs with chymopapain. Spine (Phila Pa 1976) 13:707-11 |
