Proteoglycans in Cartilage

- See: cartilage topics

- Discussion:
    - proteoglycan is a macromolecule constructed of a protein core to which many glycosaminoglycan chains are attached - protein with
           bound side chains (glycosaminoglycans);
           - to this proteoglycan aggregate, hyaluronic acid is non covalently bound;
           - in osteoarthritis, there is a characteristic reduction in a aggregrating proteoglycans;
    - about 10% of wt of proteoglycan molecule is protein, and 90% is glycosaminoglycans;
    - proteoglycans carry fixed negative charges and attract a high concentration of cations;
    - glycans: negatively chondroitin & keratan sulfate repel each other, so that glycosaminoglycan electrostaticrepulsion along chain
           and between chains and therefore chains assume a fully extended conformation;
    - sub-types:
           - aggrecans (large agregating proteoglycans)
                 - key proteoglycan molecule in the cartilage matrix and creates the osmotic properties necessary for cartilage  to resist
                         compressive loads;
           - small proteoglycans (decorin (coats the outside of the collagen fibrils), biglycan, and fibromodulin);
    - link protein:
           - small glycoprotein serves to stabilize non-covalent association of the proteoglycan subunits with hyaluronic acid in aggregate;
    - protein core:
           - approximately 100 chondroitin sulfate  and 50 keratan sulfate chains are attached;

    - aggrecan:
           - major proteoglycan in cartilage, linked to hyaluronan;
           - provides unique capacity to bear load and resist compression
           - hydrated and thereby allows cartilage to resist a compressive load
           - loss of aggrecan is the primary event leading to the destruction of cartilage;
           - aggrecanases: enzymes which degrate aggrencans;
                  - ADAMTS (a disintegrin and metalloproteinase) family of proteinases
                  - aggrecanase-1 and aggrecanase-2

The chondrocyte: a cell under pressure.

Regulation of matrix synthesis rates by the ionic and osmotic environment of articular chondrocytes.

Synthesis of chondrocytic keratan sulphate-containing proteoglycans by human chondrosarcoma cells in long-term cell culture.

Ultrastructural modifications of proteoglycans coincident with mineralization in local regions of rat growth plate.

Electron microscopic studies of cartilage proteoglycans: Direct evidence for the variable length of the chondroitin sulfate-rich region of proteoglycan subunit core protein.
Assembly of newly synthesized proteoglycan and link protein into aggregates in cultures of chondrosarcoma chondrocytes.

Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon.

Expression of a Wide Range of Extracellular Matrix Molecules in the Tendon and Trochlea of the Human Superior Oblique Muscle

Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Wednesday, July 6, 2016 3:41 am