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Biochimica et biophysica acta2003; 1622(3); 161-168; doi: 10.1016/s0304-4165(03)00138-7

The effect of link peptide on proteoglycan synthesis in equine articular cartilage.

Abstract: The basal rate of in vitro proteoglycan (PG) synthesis in explants of equine articular cartilage was subject to considerable variation in animals of the same age but was greater in younger than older animals. Synthesis of PGs in explant cultures was stimulated by a synthetic link peptide, identical in sequence to the N-terminus of the link protein (LP) of PG aggregates, in a similar manner to that demonstrated previously for human articular cartilage [Biochem. Soc. Trans. 25 (1997) 427; Arthritis Rheum. 41 (1998) 157]. Stimulation occurred in tissue from animals ranging from 1 to 30 years old but older animals required higher concentrations of peptide to produce a measurable response. Synthesis of PGs increased in a concentration-dependent manner and was paralleled by increases in the ability of aggrecan monomers to form aggregates with hyaluronan (HA). In addition to its effect on synthesis of PGs, link peptide also increased synthesis of both aggrecan and LP mRNA. Cartilage explant and chondrocyte cultures secreted small amounts of biologically active interleukin 1 (IL 1) and secretion of this cytokine was reduced considerably by the addition of link peptide. Reduction in the activity of this catabolic cytokine coupled with the increased synthesis of mRNA for aggrecan and link peptide may be the mechanism by which link peptide exerts its positive effect on the rate of PG synthesis in articular cartilage.
Publication Date: 2003-08-21 PubMed ID: 12928112DOI: 10.1016/s0304-4165(03)00138-7Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study explores the influence of a synthetic link peptide on proteoglycan production in horse articular cartilage. The research indicates that the peptide can stimulate proteoglycan synthesis, particularly in younger animals, and may prove useful in reducing the effects of age-related joint degeneration.

Variation in Proteoglycan Synthesis Among Different Age Groups

  • The research begins by observing the variable rate of proteoglycan synthesis in vitro in equine articular cartilage explants, particularly noting discrepancies among animals of the same age.
  • It is observed that younger animals demonstrate greater rates of proteoglycan synthesis than older animals. This could potentially relate to natural physiological mechanisms that decrease with age, but the study does not delve deeper into this aspect.

Effects of Synthetic Link Peptide on Proteoglycan Synthesis

  • The central aspect of this study involves exploring the impact of a synthetic link peptide on the production of proteoglycans.
  • The link peptide in this case is synonymous with the N-terminus of the link protein of proteoglycan aggregates; an aspect that has been previously confirmed with human articular cartilage.
  • The peptide’s influence is observed across different ages of animals, from 1 to 30 years old. However, higher concentrations of the peptide are required for older animals to produce a measurable response.

Concentration-Dependent Response and Stimulation of Aggrecan and Link Protein mRNA Synthesis

  • The study also notes a concentration-dependent response wherein increased levels of this peptide correlate with heightened proteoglycan synthesis.
  • This response also enhances the capability of aggrecan monomers to form aggregates with hyaluronan, a vital component in joint health.
  • The presence of the synthetic link peptide additionally stimulates the synthesis of aggrecan and Link Protein (LP) mRNA – a key step in the production of proteins essential for cartilage health.

Modulation of Interleukin 1 secretion

  • The study also finds that the peptide hampers the secretion of interleukin 1, a cytokine associated with catabolic activities that can potentially harm articular cartilage.
  • This effect, combined with the stimulated synthesis of proteins and mRNA due to the peptide, could be the mechanism behind the positive influence on proteoglycan synthesis rates in articular cartilage.

To summarise, this study reveals the potential of synthetic link peptide in positively influencing proteoglycan synthesis, especially in younger animals. With a lower rate of proteoglycan synthesis being a characteristic of aging cartilage, the peptide could offer therapeutic applications in managing age-related joint degeneration.

Cite This Article

APA
Dean MF, Lee YW, Dastjerdi AM, Lees P. (2003). The effect of link peptide on proteoglycan synthesis in equine articular cartilage. Biochim Biophys Acta, 1622(3), 161-168. https://doi.org/10.1016/s0304-4165(03)00138-7

Publication

ISSN: 0006-3002
NlmUniqueID: 0217513
Country: Netherlands
Language: English
Volume: 1622
Issue: 3
Pages: 161-168

Researcher Affiliations

Dean, M F
  • Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK. mdean@rvc.ac.uk
Lee, Y W
    Dastjerdi, A M
      Lees, P

        MeSH Terms

        • Age Factors
        • Aggrecans
        • Amino Acid Sequence
        • Animals
        • Cartilage, Articular / drug effects
        • Cartilage, Articular / metabolism
        • Chondrocytes / drug effects
        • Chondrocytes / metabolism
        • Dose-Response Relationship, Drug
        • Extracellular Matrix Proteins
        • Horses
        • Lectins, C-Type
        • Molecular Sequence Data
        • Peptide Fragments / pharmacology
        • Proteins / pharmacology
        • Proteoglycans / biosynthesis
        • Proteoglycans / genetics
        • RNA, Messenger / analysis

        Citations

        This article has been cited 1 times.
        1. Roberts JJ, Nicodemus GD, Giunta S, Bryant SJ. Incorporation of biomimetic matrix molecules in PEG hydrogels enhances matrix deposition and reduces load-induced loss of chondrocyte-secreted matrix. J Biomed Mater Res A 2011 Jun 1;97(3):281-91.
          doi: 10.1002/jbm.a.33057pubmed: 21442729google scholar: lookup