Abstract/Details

The structure and biosynthesis of human intervertebral disc proteoglycans

Johnstone, B.   University of London, Institute of Orthopaedics (United Kingdom) ProQuest Dissertations & Theses,  1988. U006492.

Abstract (summary)

The proteoglycans of the intervertebral disc exert a high swelling pressure, which is responsible for the hydration of the tissue and therefore, have an important role in the behaviour of the disc as a load-bearing tissue. Very little is known of proteoglycan synthesis in the disc, and therefore of the relationship between proteoglycan content and turnover, partly because the disc swells and loses proteoglycans when excised and placed in culture medium making in vitro studies difficult. An in vitro culture method was developed that overcame these problems and was used to measure proteoglycan synthesis rates in rabbit, dog and human discs. In vitro determined rates for the animal discs compared well with those of in vivo studies. The rate was highest in the nucleus of discs of all three species. The rate varied with position across the human annulus and showed an age-related shift in maximal activity; from the inner annulus of foetal discs to the mid-annulus of adult discs. The rate of proteoglycan synthesis also varied with change in hydration and was highest at hydrations closest to those in vivo. The rate decreased sharply if the tissue was swollen or dehydrated, but the decrease was reversible. Since the hydration of human discs changes by up to 20% during daily activity, the effect on the proteoglycan synthesis rate has important physiological implications. The structure of newly-synthesised proteoglycans and their extracellular assembly at different ages was also investigated using the in vitro culture system. Both newly-synthesised and unlabelled proteoglycans from young normal discs were highly aggregated and were stable to competition with oligomers of hyaluronic acid, indicating that functional link proteins were present. There was an age-related decrease in aggregate stability. In the annulus and nucleus of discs between 9 years and 60 years of age, the proportion of aggregated proteoglycans decreased. However, the newly-synthesised proteoglycans aggregated after a period of `chase' incubation and thus exhibited a `delayed aggregation' phenomenon. Structural analyses revealed an age-related increase in the heterogeneity of unlabelled proteoglycans but no change in the size of the newly-synthesised molecules. Immunoblotting of proteoglycans separated by agarose-polyacrylamide gel electrophoresis indicated that the composition of the non-aggregated population was such that it may be formed from turnover of aggregated proteoglycans. Hence the observed heterogeneity probably results from accumulation in the matrix of normal proteoglycan turnover products rather than synthesis of different core proteins.

Indexing (details)


Subject
Morphology
Classification
0287: Morphology
Identifier / keyword
(UMI)AAIU006492; Biological sciences
Title
The structure and biosynthesis of human intervertebral disc proteoglycans
Author
Johnstone, B.
Number of pages
1
Degree date
1988
School code
8477
Source
DAI-C 70/02, Dissertation Abstracts International
University/institution
University of London, Institute of Orthopaedics (United Kingdom)
University location
England
Degree
Ph.D.
Source type
Dissertation or Thesis
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
U006492
ProQuest document ID
301492818
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
https://www.proquest.com/docview/301492818