Effect of age on the abundance and fragmentation of link protein of the human intervertebral disc

Pearce, R. H.; Mathieson, J.; Mort, John S.; Roughley, Peter J.

doi:10.1002/jor.1100070612

Cited by 32 publications

(23 citation statements)

References 19 publications

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“…With the advent of new technology used here to study type II collagen denaturation, we now know that there is increased damage to collagen fibrils in normal adult discs compared with hyaline cartilage (34). Recent studies of human discs have also revealed increased cleavage of link protein (35) accompanying the loss of aggrecan aggregation (36) and an overall reduction in the content of these molecules with age (35)(36)(37)(38). However, these studies did not distinguish between growth, maturation, ageing, and disc degeneration.…”

Section: Discussionmentioning

confidence: 99%

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Antoniou

Steffen²,

Nelson³

et al. 1996

J. Clin. Invest.

949

842

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Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration.Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly.The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs.We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type II collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration. ( J. Clin. Invest. 1996. 98:996-1003.)

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Section: Discussionmentioning

confidence: 99%

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Antoniou

Steffen²,

Nelson³

et al. 1996

J. Clin. Invest.

949

842

View full text Add to dashboard Cite

show abstract

“…It stabilizes the aggregates by binding to both aggrecan and hyaluronic acid. [2][3][4] The presence of Link protein in cartilage [2][3][4][5] and IVD 6 suggests a common function of providing structural stability to proteoglycan-hyaluronan aggregates in both tissues.…”

Section: Introductionmentioning

confidence: 97%

Effect of Synthetic Link N Peptide on the Expression of Type I and Type II Collagens in Human Intervertebral Disc Cells

Petit

Yao

Rowas

et al. 2011

Tissue Engineering Part A

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Intervertebral disc (IVD) degeneration is associated with proteolytic degradation of proteoglycan aggregates present within the extracellular matrix of the disc. Link N peptide (DHLSDNYTLDHDRAIH) is the N-terminal peptide of link protein, which stabilizes the proteoglycan aggregates. It is generated in vivo by proteolytic degradation during tissue turnover. It has been previously shown that this peptide can stimulate the synthesis of collagens by articular cartilage and bovine IVD cells in vitro. Being a synthetic peptide, Link N has considerable financial benefits for clinical use over recombinant growth factors because it is extremely cheap to produce. The purpose of the present study was to determine the effect of Link N on the expression of types I and II collagen and investigate the cellular mechanisms of Link N signal transduction in human IVD cells. The present results suggest that Link N stimulates the expression of types I and II collagen in human IVD cells. More specifically, Link N stimulated the expression of type I in nucleus pulposus (NP) cells, but not in annulus fibrosus cells. As Link N also decreased the phosphorylation of p38 in NP cells only, results suggest that p38 is a mediator of the effect of Link N on type I collagen expression. p38 is a member of the mitogen-activated protein kinase family highlighted by three major cascades: p38, c-Jun amino-terminal kinase, and extracellular signal-regulated kinase pathways. Link N showed no effect on the latter two pathways, suggesting a specific effect of Link N on the p38 cascade. On the other hand, Link N stimulated the expression of type II collagen in both NP and annulus fibrosus, suggesting that other mechanisms are implicated in the control of type II collagen expression in disc cells, without excluding p38 for the NP. In conclusion, the present study showed that Link N can modulate the expression of collagen in human IVD cells.

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“…In parallel, ECM's degradation is also increased in NP of aged individuals (Jahnke and McDevitt, 1988;Sztrolovics et al, 1997). A tight collagen network with high proportion of proteoglycan content is found in younger discs and provides fluid flow (Pearce et al, 1989;Krajickova et al, 1995).…”

mentioning

confidence: 96%

Tissue‐engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF‐β1 in platelet‐rich plasma

Chen

Lee

et al. 2006

Journal Cellular Physiology

131

116

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Human intervertebral disc (IVD) degeneration often initiated from the human nucleus pulposus (hNP) with aging leading to IVD destruction and extracellular matrix (ECM) depletion. Previously, we have successfully employed transforming growth factor-beta1 (TGF-beta1) to promote chondrogenesis of mesenchymal progenitor cells (MPCs) and immortalized human mesenchymal stem cells. In this study, we examine the role of TGF-beta1 in platelet-rich plasma (PRP) on disc regeneration, including proliferation, redifferentiation, and the reconstitution of tissue-engineered NP. hNP cells were isolated from volunteers with different ages and cultured in the presence of PRP. We found that the most effective concentration for hNP proliferation was 1 ng/ml TGF-beta1 in PRP, which was further applied in the following experiments. hNP cell proliferation in all age groups were increased time-dependently by PRP and cell morphologies showed aggregation. The mRNA of Sox9, type II collagen, and aggrecan were all significantly upregulated by PRP through RT-PCR. Glycosaminoglycan (GAG) accumulation reached the highest value at day 7 and continued to day 9 culture. PRP promoted NP regeneration via the Smad pathway was also determined and highly activated p-Smad2/3 at 30 min and continuously sustained to 120 min. Immunostaining of type II collagen indicates that PRP participates in chondrogenesis of tissue-engineered NP with collagen scaffolds. We concluded that growth factors in PRP can effectively react as a growth factor cocktail to induce hNP proliferation and differentiation, and also promote tissue-engineered NP formation. These findings are the first to demonstrate that PRP might be a therapeutic candidate for prevention of disc degeneration.

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Effect of age on the abundance and fragmentation of link protein of the human intervertebral disc

Cited by 32 publications

References 19 publications

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Effect of Synthetic Link N Peptide on the Expression of Type I and Type II Collagens in Human Intervertebral Disc Cells

Tissue‐engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF‐β1 in platelet‐rich plasma

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