Cartilage proteoglycans: Structure and potential functions

Hyaline cartilage contains five well‐characterized proteoglycans in its extracellular matrix, and it is likely that others exist. The largest in size and most abundant by weight is aggrecan, a proteoglycan that possesses over 100 chondroitin sulfate and keratan sulfate chains. Aggrecan is also characterized by its ability to interact with hyaluronic acid to form large proteoglycan aggregates. Both the high anionic charge on the individual aggrecan molecules endowed by the sulfated glycosaminoglycan chains and the localization within the matrix endowed by aggregate formation are essential for aggrecan function. The molecule provides cartilage with its osmotic properties, which give articular cartilage its ability to resist compressive loads. The other proteoglycans are characterized by their ability to interact with collagen. They are much smaller than aggrecan in size but may be present in similar molar amounts. Decorin, biglycan, and fibromodulin are closely related in protein structure but differ in glycosaminoglycan composition and function. Decorin and biglycan possess one and two dermatan sulfate chains, respectively, whereas fibromodulin bears several keratan sulfate chains. Decorin and fibromodulin both interact with the type II collagen fibrils in the matrix and may play a role in fibrillogenesis and interfibril interactions. Biglycan is preferentially localized in the pericellular matrix, where it may interact with type VI collagen. Finally, type IX collagen can also be considered as a proteoglycan, as its α2(IX) chain may bear a glycosaminoglycan chain. It may serve as a bridge between the collagen fibrils or with the interspersed aggrecan network. © 1994 Wiley‐Liss, Inc.

[1]  P. Roughley,et al.  Non-proteoglycan forms of biglycan increase with age in human articular cartilage. , 1993, The Biochemical journal.

[2]  X. Chen,et al.  Assignment of the human aggrecan gene (AGC1) to 15q26 using fluorescence in situ hybridization analysis. , 1993, Genomics.

[3]  P. Roughley,et al.  Versican gene expression in human articular cartilage and comparison of mRNA splicing variation with aggrecan. , 1993, The Biochemical journal.

[4]  A. Poole,et al.  Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. , 1992, The Journal of clinical investigation.

[5]  M. Lark,et al.  In vivo expression of stromelysin in synovium and cartilage of rabbits injected intraarticularly with interleukin-1 beta. , 1992, Arthritis and rheumatism.

[6]  T. Hardingham,et al.  The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B. , 1992, The Journal of biological chemistry.

[7]  R. Miehlke,et al.  Presence of small proteoglycan fragments in normal and arthritic human cartilage. , 1992, Arthritis and rheumatism.

[8]  S. S. Hughes,et al.  Nonradioactive in situ hybridization using digoxigenin-labeled oligonucleotides. Applications to musculoskeletal tissues. , 1992, The American journal of pathology.

[9]  P. Roughley,et al.  Monoclonal antibodies recognizing protease-generated neoepitopes from cartilage proteoglycan degradation. Application to studies of human link protein cleavage by stromelysin. , 1992, The Journal of biological chemistry.

[10]  M. Mörgelin,et al.  Variability in the G3 domain content of bovine aggrecan from cartilage extracts and chondrocyte cultures. , 1992, Archives of biochemistry and biophysics.

[11]  C. Kielty,et al.  Type VI collagen microfibrils: evidence for a structural association with hyaluronan , 1992, The Journal of cell biology.

[12]  K. Kuettner,et al.  Biochemistry of articular cartilage in health and disease. , 1992, Clinical biochemistry.

[13]  P. Roughley,et al.  Preferential mRNA expression of prostromelysin relative to procollagenase and in situ localization in human articular cartilage. , 1992, The Journal of clinical investigation.

[14]  H. C. Robinson,et al.  Mechanism of catabolism of aggrecan by articular cartilage. , 1992, Archives of biochemistry and biophysics.

[15]  T. Hardingham,et al.  Proteoglycans: many forms and many functions , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  J. Vergnes,et al.  cDNA to chick lumican (corneal keratan sulfate proteoglycan) reveals homology to the small interstitial proteoglycan gene family and expression in muscle and intestine. , 1992, The Journal of biological chemistry.

[17]  S. Mundlos,et al.  Distribution of cartilage proteoglycan (aggrecan) core protein and link protein gene expression during human skeletal development. , 1991, Matrix.

[18]  A. Marriott,et al.  Mammalian cartilage synthesizes both proteoglycan and non-proteoglycan forms of type IX collagen. , 1991, The Biochemical journal.

[19]  P. Roughley,et al.  Link protein as a monitor in situ of endogenous proteolysis in adult human articular cartilage. , 1991, The Biochemical journal.

[20]  M. Young,et al.  Human biglycan gene. Putative promoter, intron-exon junctions, and chromosomal localization. , 1991, The Journal of biological chemistry.

[21]  A. Poole,et al.  Characterization of aggregating proteoglycans from the proliferative, maturing, hypertrophic, and calcifying zones of the cartilaginous physis. , 1991, The Journal of bone and joint surgery. American volume.

[22]  J. Sandy,et al.  Analysis of the catabolism of aggrecan in cartilage explants by quantitation of peptides from the three globular domains. , 1991, The Journal of biological chemistry.

[23]  R L Jackson,et al.  Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. , 1991, Physiological reviews.

[24]  T. Hardingham,et al.  1-C-6 epitope in cartilage proteoglycan G2 domain is masked by keratan sulphate. , 1991, The Biochemical journal.

[25]  K. Doege,et al.  Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms. , 1991, The Journal of biological chemistry.

[26]  A. Plaas,et al.  Identification of the keratan sulfate attachment sites on bovine fibromodulin. , 1990, The Journal of biological chemistry.

[27]  R. Eddy,et al.  Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene. , 1990, Genomics.

[28]  M. Young,et al.  Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[29]  D. Heinegård,et al.  Structure and function of extracellular matrix proteoglycans. , 1990, Biochemical Society transactions.

[30]  Y. Yamada,et al.  Rat and human cartilage proteoglycan (aggrecan) gene structure. , 1990, Biochemical Society transactions.

[31]  T. Hardingham,et al.  The primary structure of human cartilage link protein. , 1990, Nucleic acids research.

[32]  O. Mcbride,et al.  Localization of PGI (biglycan, BGN) and PGII (decorin, DCN, PG-40) genes on human chromosomes Xq13-qter and 12q, respectively. , 1990, Genomics.

[33]  E. Quentin,et al.  A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[34]  E. Ruoslahti,et al.  Multiple domains of the large fibroblast proteoglycan, versican. , 1989, The EMBO journal.

[35]  P. Roughley,et al.  Dermatan sulphate proteoglycans of human articular cartilage. The properties of dermatan sulphate proteoglycans I and II. , 1989, The Biochemical journal.

[36]  D. Heinegård,et al.  A collagen‐binding 59‐kd protein (fibromodulin) is structurally related to the small interstitial proteoglycans PG‐S1 and PG‐S2 (decorin). , 1989, The EMBO journal.

[37]  T. Hardingham,et al.  Isolation of the N-terminal globular protein domains from cartilage proteoglycans. Identification of G2 domain and its lack of interaction with hyaluronate and link protein. , 1989, The Biochemical journal.

[38]  D. Heinegård,et al.  Shared and distinct structural features of interstitial proteoglycans from different bovine tissues revealed by electron microscopy. , 1989, The Journal of biological chemistry.

[39]  P. Roughley,et al.  The synthesis of dermatan sulphate proteoglycans by fetal and adult human articular cartilage. , 1989, The Biochemical journal.

[40]  R. Stockwell,et al.  Keratan sulphate: a functional substitute for chondroitin sulphate in O2 deficient tissues? , 1989, Pathologie-biologie.

[41]  L. Rosenberg,et al.  The primary structure of the core protein of the small, leucine-rich proteoglycan (PG I) from bovine articular cartilage. , 1989, The Journal of biological chemistry.

[42]  D. Heinegård,et al.  Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. , 1989, The Journal of biological chemistry.

[43]  M. Young,et al.  Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species. , 1989, The Journal of biological chemistry.

[44]  L. Tang,et al.  Characterization of the dermatan sulfate proteoglycans, DS-PGI and DS-PGII, from bovine articular cartilage and skin isolated by octyl-sepharose chromatography. , 1989, The Journal of biological chemistry.

[45]  D. Howell,et al.  Superficial and deeper layers of dog normal articular cartilage. Role of hyaluronate and link protein in determining the sedimentation coefficients distribution of the nondissociatively extracted proteoglycans. , 1988, The Journal of biological chemistry.

[46]  P. Mourão,et al.  Distribution of chondroitin 4-sulfate and chondroitin 6-sulfate in human articular and growth cartilage. , 1988, Arthritis and rheumatism.

[47]  J. Scott.  Proteoglycan-fibrillar collagen interactions. , 1988, The Biochemical journal.

[48]  L. Vaughan,et al.  D-periodic distribution of collagen type IX along cartilage fibrils , 1988, The Journal of cell biology.

[49]  H. Muir,et al.  Hyaluronic acid in human articular cartilage. Age-related changes in content and size. , 1988, The Biochemical journal.

[50]  Y. Yamada,et al.  Complete primary structure of the rat cartilage proteoglycan core protein deduced from cDNA clones. , 1987, The Journal of biological chemistry.

[51]  T. Koob,et al.  Characterization and interactions of a fragment of the core protein of the small proteoglycan (PGII) from bovine tendon. , 1987, Biochemical and biophysical research communications.

[52]  P. Roughley,et al.  The Structure and Abundance of Cartilage Proteoglycans during Early Development of the Human Fetus , 1987, Pediatric Research.

[53]  J. Périn,et al.  Link protein interactions with hyaluronate and proteoglycans. Characterization of two distinct domains in bovine cartilage link proteins. , 1987, The Journal of biological chemistry.

[54]  I. Kiss,et al.  Structure of the chicken link protein gene: exons correlate with the protein domains. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[55]  R. Timpl,et al.  Extended and globular protein domains in cartilage proteoglycans. , 1987, The Biochemical journal.

[56]  J. Trotter,et al.  The effect of proteoglycans on the morphology of collagen fibrils formed in vitro. , 1987, Collagen and related research.

[57]  B. Olsen,et al.  Structure of the glycosaminoglycan domain in the type IX collagen-proteoglycan. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[58]  E. Ruoslahti,et al.  Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[59]  P. Roughley,et al.  Ageing and the aggregating proteoglycans of human articular cartilage. , 1986, Clinical science.

[60]  M. Lyon,et al.  Structure and function of heparan sulphate proteoglycans. , 1986, The Biochemical journal.

[61]  L. Rosenberg,et al.  Localization of a dermatan sulfate proteoglycan (DS-PGII) in cartilage and the presence of an immunologically related species in other tissues. , 1986, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[62]  P. Neame,et al.  The primary structure of link protein from rat chondrosarcoma proteoglycan aggregate. , 1986, The Journal of biological chemistry.

[63]  J. Scott.  Proteoglycan histochemistry--a valuable tool for connective tissue biochemists. , 1985, Collagen and related research.

[64]  P. Scott,et al.  Dermatan sulphate is located on serine-4 of bovine skin proteodermatan sulphate. Demonstration that most molecules possess only one glycosaminoglycan chain and comparison of amino acid sequences around glycosylation sites in different proteoglycans. , 1985, The Biochemical journal.

[65]  L. Tang,et al.  Proteoglycans from bovine nasal and articular cartilages. Fractionation of the link proteins by wheat germ agglutinin affinity chromatography. , 1985, The Journal of biological chemistry.

[66]  P. Roughley,et al.  Identification of a hyaluronic acid-binding protein that interferes with the preparation of high-buoyant-density proteoglycan aggregates from adult human articular cartilage. , 1985, The Biochemical journal.

[67]  D. Heinegård,et al.  Characterization of proteoglycans from adult bovine tendon. , 1985, The Journal of biological chemistry.

[68]  B. Toole,et al.  Pericellular coat of chick embryo chondrocytes: structural role of hyaluronate , 1984, The Journal of cell biology.

[69]  E. Hunziker,et al.  Cartilage ultrastructure after high pressure freezing, freeze substitution, and low temperature embedding. II. Intercellular matrix ultrastructure - preservation of proteoglycans in their native state , 1984, The Journal of cell biology.

[70]  P. Roughley,et al.  Age-related changes in the structure of proteoglycan link proteins present in normal human articular cartilage. , 1983, The Biochemical journal.

[71]  S. Lohmander,et al.  Structures of N-linked and O-linked oligosaccharides on proteoglycan monomer isolated from the Swarm rat chondrosarcoma. , 1982, The Journal of biological chemistry.

[72]  P. Roughley,et al.  O-Linked oligosaccharides of human articular cartilage proteoglycan. , 1982, Biochimica et biophysica acta.

[73]  A R Poole,et al.  An immunoelectron microscope study of the organization of proteoglycan monomer, link protein, and collagen in the matrix of articular cartilage , 1982, The Journal of cell biology.

[74]  A. Malmström,et al.  Biosynthesis of dermatan sulphate. Assay and properties of the uronosyl C-5 epimerase. , 1982, The Biochemical journal.

[75]  H. Barrach,et al.  Absence of proteoglycan core protein in cartilage from the cmd/cmd (cartilage matrix deficiency) mouse. , 1981, The Journal of biological chemistry.

[76]  J. Buckwalter,et al.  The presence of a cartilage-like proteoglycan in the adult human meniscus. , 1981, The Biochemical journal.

[77]  J. Buckwalter,et al.  Structural changes during development in bovine fetal epiphyseal cartilage. , 1981, Collagen and related research.

[78]  T. Hardingham,et al.  Assembly of newly synthesized proteoglycan and link protein into aggregates in cultures of chondrosarcoma chondrocytes. , 1980, The Journal of biological chemistry.

[79]  L. Cöster,et al.  Interaction between dermatan sulphate chains. II. Structural studies on aggregating glycan chains and oligosaccharides with affinity for dermatan sulphate-substituted agarose. , 1979, Biochimica et biophysica acta.

[80]  S. Lee-Huang,et al.  Isolation and characterization of proteoglycans from human chondrosarcomas. , 1978, The Journal of biological chemistry.

[81]  N. Mitchell,et al.  The localization of articular cartilage proteoglycan by electron microscopy , 1977, The Anatomical record.

[82]  R. Giugliani,et al.  The mucopolysaccharidoses. , 1976, Journal of medical genetics.

[83]  H. Rogers,et al.  Biosynthesis of Hyaluronate , 1955, Nature.

[84]  P. Roughley,et al.  Changes in the expression of decorin and biglycan in human articular cartilage with age and regulation by TGF-beta. , 1994, Matrix biology : journal of the International Society for Matrix Biology.

[85]  R. Iozzo,et al.  The human decorin gene: intron-exon organization, discovery of two alternatively spliced exons in the 5' untranslated region, and mapping of the gene to chromosome 12q23. , 1993, Genomics.

[86]  P. Roughley,et al.  Proteolytic degradation in human articular cartilage: its relationship to stromelysin. , 1993, Agents and actions. Supplements.

[87]  M. Young,et al.  Human decorin gene: intron-exon junctions and chromosomal localization. , 1993, Genomics.

[88]  K. Brandt,et al.  Hypothesis: can type IX collagen "glue" together intersecting type II fibers in articular cartilage matrix? A proposed mechanism. , 1992, The Journal of rheumatology.

[89]  B. Olsen,et al.  FACIT collagens: diverse molecular bridges in extracellular matrices. , 1991, Trends in biochemical sciences.

[90]  M. Takagi.  Ultrastructural cytochemistry of cartilage proteoglycans and their relation to the calcification process , 1990 .

[91]  C. P. Morris,et al.  The mucopolysaccharidoses. Diagnosis, molecular genetics and treatment. , 1990, Molecular biology & medicine.

[92]  K. Vogel,et al.  Characteristics of the in vitro interaction of a small proteoglycan (PG II) of bovine tendon with type I collagen. , 1989, Matrix.

[93]  L. Tang,et al.  Proteoglycans from bovine fetal epiphyseal cartilage. Sedimentation velocity and light scattering studies of the effect of link protein on proteoglycan aggregate size and stability. , 1989, Connective tissue research.

[94]  B. Olsen.  The next frontier: molecular biology of extracellular matrix. , 1989, Connective tissue research.

[95]  E. Hunziker,et al.  Structural Organization of Proteoglycans in Cartilage , 1987 .

[96]  J. Scott,et al.  Proteoglycan-type I collagen fibril interactions in bone and non-calcifying connective tissues , 1985, Bioscience reports.

[97]  N. Schwartz.  Defect in proteoglycan synthesis in brachymorphic mice. , 1982, Progress in clinical and biological research.

[98]  V. Hascall.  Structure and biosynthesis of proteoglycans with keratan sulfate. , 1982, Progress in clinical and biological research.

[99]  T. Hardingham.  The role of link-protein in the structure of cartilage proteoglycan aggregates. , 1979, The Biochemical journal.

[100]  M. Höök,et al.  Biosynthesis of heparin. , 1975, Advances in experimental medicine and biology.

[101]  T. Liu,et al.  Cyclopropane ring blosynthesis. , 1962, Biochemistry.