Hyaluronate degradation as an alternative mechanism for proteoglycan release from cartilage during interleukin-1β-stimulated catabolism

2002 ◽  
Vol 362 (2) ◽  
pp. 473-479 ◽  
Author(s):  
Robert SZTROLOVICS ◽  
Anneliese D. RECKLIES ◽  
Peter J. ROUGHLEY ◽  
John S. MORT
Keyword(s):  
Core Protein ◽  
Cartilage Matrix ◽  
Interleukin 1Β ◽  
Alternative Mechanism ◽  
Human Articular Cartilage ◽  
Link Protein ◽  
Nasal Cartilage ◽  
Fetal Bovine ◽  
Proteoglycan Release ◽  
Aggrecan Core Protein

Data presented previously suggest that release of components of the cartilage matrix, in response to catabolic agents, cannot be accounted for by proteolytic mechanisms alone. In the present study, the release of glycosaminoglycan-containing components from bovine nasal cartilage cultured in the presence of interleukin-1β, and from bovine nasal, fetal bovine epiphyseal and adult human articular cartilage cultured in the presence of retinoic acid, was accompanied by the loss of link protein and hyaluronate into the culture medium. Chromatographic analysis of the released hyaluronate showed it to be markedly reduced in size relative to that extracted from the corresponding tissue. It is proposed that, under stimulation by catabolic agents, two independent, but concurrent, mechanisms act to promote the release of aggrecan from the cartilage matrix. First, proteolytic cleavage of the aggrecan core protein results in the production of glycosaminoglycan-containing fragments that are free to diffuse from the tissue. Secondly, cleavage of hyaluronate renders portions of the proteoglycan aggregate small enough so that complexes of aggrecan (or fragments containing its G1 domain) and link protein are released from the tissue. It is likely that both mechanisms contribute to cartilage metabolism in normal physiology and pathology.

scholarly journals Demonstration of link protein in proteoglycan aggregates from human intervertebral disc

1984 ◽  
Vol 222 (1) ◽  
pp. 85-92 ◽  
Author(s):  
A Tengblad ◽  
R H Pearce ◽  
B J Grimmer
Keyword(s):  
Intervertebral Disc ◽  
Density Gradient ◽  
Gradient Centrifugation ◽  
Buoyant Density ◽  
Intervertebral Discs ◽  
Human Articular Cartilage ◽  
Link Protein ◽  
Nasal Cartilage ◽  
Proteoglycan Aggregates ◽  
Cartilage Proteoglycans

Proteoglycan aggregates free of non-aggregating proteoglycan have been prepared from the annuli fibrosi and nuclei pulposi of intervertebral discs of three human lumbar spines by extraction with 4M-guanidinium chloride, associative density gradient centrifugation, and chromatography on Sepharose CL-2B. The aggregate (A1-2B.V0) was subjected to dissociative density-gradient ultracentrifugation. Three proteins of Mr 38 900, 44 200 and 50 100 found in the fraction of low buoyant density (A1-2B.V0-D4) reacted with antibodies to link protein from newborn human articular cartilage. After reduction with mercaptoethanol, two proteins of Mr 43 000 and two of Mr 20 000 and 14 000 were seen. The A1-2B.V0-D4 fraction, labelled with 125I, coeluted with both hyaluronate and a hyaluronate oligosaccharide (HA14) on a Sepharose CL-2B column. HA10 and HA14 reduced the viscosity of A1 fractions; HA4, HA6 and HA8 did not. HA14 decreased the viscosity of disc proteoglycans less than it did that of bovine cartilage proteoglycans. Thus, although a link protein was present in human intervertebral disc, it stabilized proteoglycan aggregates less well than did the link protein from bovine nasal cartilage.

Localization of the Expression of Type I, II, III Collagen, and Aggrecan Core Protein Genes in Developing Human Articular Cartilage

Matrix ◽  
1992 ◽  
Vol 12 (3) ◽  
pp. 221-232 ◽  
Author(s):  
Isabelle Treilleux ◽  
Frederic Mallein-Gerin ◽  
Dominique Le Guellec ◽  
Daniel Herbage
Keyword(s):  
Articular Cartilage ◽  
Core Protein ◽  
Type I ◽  
Human Articular Cartilage ◽  
Aggrecan Core Protein

scholarly journals Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability

1998 ◽  
Vol 337 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Mark C. BOLTON ◽  
Jayesh DUDHIA ◽  
Michael T. BAYLISS
Keyword(s):  
Articular Cartilage ◽  
De Novo ◽  
Core Protein ◽  
Buoyant Density ◽  
Aggregate Stability ◽  
Exchange Chromatography ◽  
Human Articular Cartilage ◽  
Post Translational Modification ◽  
Link Protein ◽  
Age Related

The rates of incorporation of radiolabelled leucine into aggrecan and link protein have been measured in human articular cartilage of different ages. Aggrecan and link protein were purified in the A1 fraction of CsCl gradients as a result of their ability to form high-buoyant-density proteoglycan aggregates with hyaluronic acid. Separation of the aggrecan from the link protein was achieved by Mono Q anion-exchange chromatography. The rates of synthesis of both aggrecan and link protein decreased with age. The age-related decrease in synthesis of aggrecan was paralleled by a decrease in the rate of sulphate incorporation into glycosaminoglycan chains. The synthesis of link protein decreased with age to a greater extent than that of aggrecan such that the ratio of the rates of link protein to aggrecan synthesis decreased from 1 in immature cartilage to 0.2 in mature cartilage. The age-related decrease in link protein synthesis is controlled at least in part by transcriptional or post-trancriptional mechanisms, as shown by the accompanying age-related decrease in link-protein mRNA. The absence of any age-related decrease in aggrecan mRNA suggests that the decrease in synthesis of aggrecan core protein is controlled by a translational mechanism. Measurement of the total tissue content of aggrecan and link protein by radioimmunoassay revealed an age-related increase in the accumulation of these matrix proteins, even though their de novo synthesis was decreasing. This illustrates the importance that the regulation of extracellular post-translational modification also has in controlling the overall turnover of the cartilage matrix.

Gene regulation during cartilage differentiation: temporal and spatial expression of link protein and cartilage matrix protein in the developing limb

Development ◽  
1989 ◽  
Vol 107 (1) ◽  
pp. 23-33
Author(s):  
N.S. Stirpe ◽  
P.F. Goetinck
Keyword(s):  
Matrix Protein ◽  
Core Protein ◽  
Type Ii Collagen ◽  
Cartilage Matrix ◽  
Type Ii ◽  
Spatial Expression ◽  
Link Protein ◽  
Genes Encoding ◽  
Temporal And Spatial ◽  
And Cartilage

The temporal and spatial expression of link protein and cartilage matrix protein genes was defined during chondrogenesis in the developing chick embryonic wing bud, using RNA in situ hybridization. For comparison, the expression of genes encoding type II collagen and cartilage proteoglycan core protein was also examined. Link protein transcripts are first detected at stage 25 of Hamburger and Hamilton, together with proteoglycan core protein transcripts. Type II collagen transcripts were first detected as early as stage 23 whereas cartilage matrix protein transcripts could not be detected before stage 26. The results of the study indicate that the temporal expression of the genes for cartilage matrix protein and type II collagen are independent of each other and also independent of that for link protein and proteoglycan core protein.

scholarly journals Hyaluronate degradation as an alternative mechanism for proteoglycan release from cartilage during interleukin-1β-stimulated catabolism

2002 ◽  
Vol 362 (2) ◽  
pp. 473 ◽  
Author(s):  
Robert SZTROLOVICS ◽  
Anneliese D. RECKLIES ◽  
Peter J. ROUGHLEY ◽  
John S. MORT
Keyword(s):  
Interleukin 1Β ◽  
Alternative Mechanism ◽  
Proteoglycan Release

scholarly journals Proteoglycans from bovine nasal cartilage. Immunochemical studies of link protein.

1980 ◽  
Vol 255 (19) ◽  
pp. 9295-9305
Author(s):  
A.R. Poole ◽  
A. Reiner ◽  
L.H. Tang ◽  
L. Rosenberg
Keyword(s):  
Link Protein ◽  
Nasal Cartilage

scholarly journals Modulation of aggrecan and link-protein synthesis in articular cartilage

1992 ◽  
Vol 288 (3) ◽  
pp. 721-726 ◽  
Author(s):  
A J Curtis ◽  
R J Devenish ◽  
C J Handley
Keyword(s):  
Articular Cartilage ◽  
Half Life ◽  
Core Protein ◽  
Calf Serum ◽  
Cartilage Explants ◽  
Dependent Manner ◽  
Link Protein ◽  
The Core ◽  
Explant Cultures ◽  
Igf I

The addition of serum or insulin-like growth factor-I (IGF-I) to the medium of explant cultures of bovine articular cartilage is known to stimulate the synthesis of aggrecan in a dose-dependent manner. The half-life of the pool of proteoglycan core protein was measured in adult articular cartilage cultured for 6 days in the presence and absence of 20 ng of IGF-I/ml and shown to be 24 min under both sets of conditions. The half-life of the mRNA pool coding for aggrecan was also determined and shown to be approx. 4 h in cartilage maintained in culture with or without IGF-I. The pool size of mRNA coding for aggrecan core protein increased 5-6-fold in cartilage explants maintained in culture in medium containing 20% (v/v) fetal-calf serum; however, in tissue maintained with medium containing IGF-I there was no increase in the cellular levels of this mRNA. This suggests that aggrecan synthesis is stimulated by IGF-I at the level of translation of mRNA coding for the core protein of this proteoglycan and that other growth factors are present in serum that stimulate aggrecan synthesis at the level of transcription of the core-protein gene. Inclusion of serum or IGF-I in the medium of cartilage explant cultures induced increases in the amounts of mRNA coding for type II collagen and link protein, whereas only serum enhanced the amount of mRNA for the core protein of decorin.

Sign in / Sign up

Export Citation Format

Share Document