The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage.
The functions of the intervertebral disc and of articular cartilage are intimately related to their aggrecan content. Aggrecan is a proteoglycan that interacts with hyaluronan to form large aggregates, which are responsible for the ability of the tissues to resist compressive loads. This function is related to the structure of aggrecan, and in particular to the large number of chondroitin sulphate chains present on its core protein. The chondroitin sulphate chains are present in two adjacent regions of the aggrecan core protein, termed the CS1 and CS2 domains. In the human, the region of the aggrecan gene encoding the CS1 domain exhibits size polymorphism, which can result in variation in the degree of chondroitin sulphate substitution of aggrecan in different individuals. This raises the possibility that the functional properties of aggrecan may vary between individuals, and that those individuals with an inferior aggrecan structure may be more susceptible to premature intervertebral disc or articular cartilage degeneration. Several studies have been performed to demonstrate such an association, but the results have been ambiguous. This review explains the relationship between aggrecan structure and function, describes the technique used to assess aggrecan polymorphism and the conclusions and limitations of the data obtained to date, and discusses the implications for tissue degeneration and clinical practice.
Roughley
P
P
Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, Quebec, Canada. proughley@shriners.mcgill.ca
Martens
D
D
Rantakokko
J
J
Alini
M
M
Mwale
F
F
Antoniou
J
J
D053674:Aggrecans; D000483:Alleles; D002358:Cartilage, Articular / Q000503:physiopathology*; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000502:physiology; D004247:DNA / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D006820:Hyaluronic Acid / Q000502:physiology; D007403:Intervertebral Disc / Q000503:physiopathology*; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D010003:Osteoarthritis / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D013122:Spinal Diseases / Q000235:genetics / Q000503:physiopathology*
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D004247:DNA