Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function.

Abstract:

:Aggrecan, a large aggregating proteoglycan, is one of the major structural components of cartilage. Its core protein contains three glubular domains and two glycosaminoglycan-attachment domains. These domains play various roles to maintain cartilage structure and function. An N-terminal globular domain binds hyaluronan and link protein to form huge aggregates. The chondroitin sulfate (CS) chains attach to the CS domain and provide a hydrated, viscous gel that absorbs compressive load. Two autosomal recessive chondrodysplasias, cartilage matrix deficiency (cmd) in mice and nanomelia in chicken are both caused by aggrecan gene mutations. Cmd homozygotes die shortly after birth, while the heterozygotes are born normal. However, cmd heterozygotes develop late onset of spinal disorder, which suggests aggrecan as a candidate gene predisposing individuals to spinal problems. Nanomelia is a useful model to elucidate intracellular trafficking of proteoglycans. Further studies on aggrecan will lead to prophylaxis and treatment of joint destructive diseases such as osteoarthrosis and to elucidation of cartilage development, which is essential for skeletal formation.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Watanabe H,Yamada Y,Kimata K

doi

10.1093/oxfordjournals.jbchem.a022166

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

687-93

issue

4

eissn

0021-924X

issn

1756-2651

journal_volume

124

pub_type

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