Elsevier

Osteoarthritis and Cartilage

Volume 2, Issue 3, September 1994, Pages 155-164
Osteoarthritis and Cartilage

Original Article
Changes in aggrecan populations in experimental osteoarthritis*

https://doi.org/10.1016/S1063-4584(05)80066-4Get rights and content

Summary

Adult articular cartilage contains at least two distinct populations of aggrecan: one is larger and richer in chondroitin sulfate (CS), while the other is smaller with less CS. The smaller form is thought to be derived from the larger. The amount of CS in cartilage decreases with maturation and aging, mainly because of a decrease in the proportion of the larger of these two proteoglycans. In early osteoarthritis (OA) the amount and concentration of CS in cartilage increases.

To test the hypothesis that an increase in the more CS-rich form of aggrecan contributes to the increase in CS in cartilage in OA, experimental OA was induced in dogs by transection of the anterior cruciate ligament, with sacrifice at various times between 2 days and 64 weeks after the operation. Proteoglycans were extracted from the articular cartilage of eight areas of the joint, fractionated, and CS was quantified by measuring hexuronate. Aggrecan populations were assessed by composite agarose-polyacrylamide gel electrophoresis.

The proportion of the more CS-rich form of aggrecan increased with time after operation in all areas of the joint. This increase correlated with increases in tissue mass and hexuronate, showing that the increase in the larger, CS-rich form of aggrecan contributes to the increase in CS in the tissue. It seems paradoxical that this form of aggrecan accumulates in the tissue despite the fact that increased protease activity has been demonstrated in experimental OA.

References (34)

  • HeinegårdD et al.

    Structure and biology of cartilage and bone matrix noncollagenous macromolecules

    FASEB J

    (1989)
  • CarneySL et al.

    The structure and funtion of cartilage proteoglycans

    Physiol Rev

    (1988)
  • SandyJD et al.

    The structure of aggrecan fragments in human synovial fluid. Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the Glu 373-Ala 374 bond of the integlobular domain

    J Clin Invest

    (1992)
  • LoulakisP et al.

    N-terminal sequence of proteoglycan fragments isolated from medium of interleukin-1-treated articular-cartilage cultures. Putative site(s) of enzymic cleavage

    Biochem J

    (1992)
  • InerotS et al.

    Proteoglycan alterations during developing experimental osteoarthritis in a novel hip joint model

    J Orthop Res

    (1991)
  • GibbonsRA

    Physicochemical methods for the determination of the purity, molecular size and shape of glycoproteins

  • RoughleyPJ et al.

    The electrophoretic heterogeneity of bovine nasal cartilage proteoglycans

    Biochem J

    (1976)
  • Cited by (4)

    • Influence of chondrocyte maturation on acute response to impact injury in PEG hydrogels

      2012, Journal of Biomechanics
      Citation Excerpt :

      Most notably, there appeared to be an age-dependent shift in the relative amount of ARG-fragment retained in the gel, and that which was released with impact loading. This observation suggests a difference in aggrecan glycosylation, which has been reported to increase during adolescence (Brown et al., 1998), but also increase in cartilage explant injury models (Adams, 1994; Chockalingam et al., 2011; Sui et al., 2009). Collagen II degradation, specifically the C1,2C collagen fragment produced by MMP-1 and MMP-13 (Garvican et al., 2010) is a biomarker of osteoarthritis and is commonly found in the synovial fluid of patients with joint injury (Lohmander et al., 2003; Mohammed et al., 2003).

    *

    Supported by The Medical Research Council of Canada and The Arthritis Society. A preliminary report of this work appeared in J Rheumatol 1987; Supplement 14:107–9, and was presented at the 1992 Annual Meeting of the American College of Rheumatology.

    View full text