Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues

Melrose, James; Fuller, Emily; Roughley, Peter J.; Smith, Margaret M.; Kerr, Briedgeen; Hughes, Claire E.; Caterson, Bruce; Little, Christopher B.

doi:10.1186/ar2453

Cited by 123 publications

(96 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, human adolescent discs (from scoliotics) showed no degradation of biglycan, decorin, fibromodulin and lumican [7]. Hence it appears that there may be a general increase in fragmentation in diseased IVDs studied here, compared to young or normal discs, similar to that seen in other degenerative joint diseases such as osteoarthritic cartilage [17].…”

Section: Discussionsupporting

confidence: 49%

“…Extraction and preparation of tissue samples for SLRP analysis SLRPs were extracted from finely diced disc tissues in 4 M GuHCl as previously described [17]. In brief the tissue The gels were electroblotted to nitrocellulose membranes (0.22 lm) either as previously described [17] using NuPAGE transfer buffer supplemented with 10% methanol at 30 V constant voltage for 1 h (Protocol 1) or transferred using an iBlot system and iBlot Gel Nitrocellulose Transfer Stacks (Invitrogen) and Program 3 (Protocol 2).…”

Section: Ivd Samplesmentioning

confidence: 99%

“…In brief the tissue The gels were electroblotted to nitrocellulose membranes (0.22 lm) either as previously described [17] using NuPAGE transfer buffer supplemented with 10% methanol at 30 V constant voltage for 1 h (Protocol 1) or transferred using an iBlot system and iBlot Gel Nitrocellulose Transfer Stacks (Invitrogen) and Program 3 (Protocol 2). SeeBlue-2 prestained protein molecular weight standards were also electrophoresed to enable calibration of molecular weights and to assess the blotting transfer efficiency.…”

Section: Ivd Samplesmentioning

confidence: 99%

“…Certainly, biglycan and fibromodulin are fragmented in models of IVD degeneration and osteoarthritis (OA) [19,35] and in articular cartilage from total knee and hip replacement patients and from menisci of OA joints [17]. SLRPs are also extensively fragmented in pathological tendon and ligament [10,24,25].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

Brown¹,

Melrose²,

Caterson³

et al. 2012

Eur Spine J

Self Cite

View full text Add to dashboard Cite

Purpose Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of the SLRP core protein species present in intervertebral discs with various pathologies. Methods Eighteen intervertebral discs from patients with scoliosis (n = 7, 19-53 years), degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58 years) were used in this study. Proteoglycans were dissociatively extracted from disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) assessed by Western blotting following deglycosylation with chondroitinase ABC and keratanase.

show abstract

Section: Discussionsupporting

confidence: 49%

Section: Ivd Samplesmentioning

confidence: 99%

Section: Ivd Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

Brown¹,

Melrose²,

Caterson³

et al. 2012

Eur Spine J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lyophilized tissue extracts were re-dissolved (2 mg dry weight/ml) overnight in 0.1 M Tris 30 mM acetate buffer (pH 6.5) at 4°C, combined to make a representative tissue extract sample, electrophoresed and blotted using previously described methods [19].…”

Section: Detection Of Stress Antigens In Ivd Tissues By Immunohistochmentioning

confidence: 99%

Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining

et al. 2009

View full text Add to dashboard Cite

Intervertebral disc (IVD) cells within the annulus fibrosus (AF) and nucleus pulposus (NP) maintain distinct functional extracellular matrices and operate within a potentially noxious and stressful environment. How disc cells respond to stress and whether stress is responsible for triggering degeneration is unknown. Disc cell proliferation and cluster formation are most marked in degenerate IVDs, possibly indicating attempts at matrix repair. In other tissues, stress proteins increase rapidly after stress protecting cell function and, although implicated in degeneration of articular cartilage, have received little attention in degenerative IVD pathologies. We have compared the distribution of stress protein immunolocalization in pathological and control IVDs. Disc tissues were obtained at surgery from 43 patients with degenerative disc disease (DDD) and herniation, and 12 controls at postmortem. Tissues were immunostained with a polyclonal antibody for heat shock factor 1 (HSF-1) and monoclonal antibodies for the heat shock proteins, Hsp27 and Hsp72, using an indirect immunoperoxidase method. Positively stained cells were expressed as a percentage of the total. Cell cluster formation was also assessed. The proportion of cells in clusters was similar in the AF (both 2%) and NP (8 and 9%) of control and DDD samples, whereas in herniated tissues this was increased (AF 12%, NP 14%). Stress antigen staining tended to be more frequent in clustered rather than in single/doublet cells, and this was significant (P \ 0.005) in both the AF and NP of herniated discs. Clustered cells, which are most common in herniated discs, may be mounting a protective response to abnormal environmental factors associated with disc degeneration. A better understanding of the stress response in IVD cells may allow its utilization in disc cell therapies.

show abstract

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Hayes

Melrose

2019

Advanced Therapeutics

Self Cite

View full text Add to dashboard Cite

The aim of this study is to review developments in glycosaminoglycan and proteoglycan research relevant to cartilage repair biology and in particular the treatment of osteoarthritis (OA). Glycosaminoglycans decorate a diverse range of extracellular matrix and cell associated proteoglycans conveying structural organization and physico-chemical properties to tissues. They play key roles mediating cellular interactions with bioactive growth factors, cytokines, and morphogenetic proteins, and structural fibrillar collagens, cell interactive and extracellular matrix proteoglycans, and glycoproteins which define tissue function. Proteoglycan degradation detrimentally affects tissue functional properties. Therapeutic strategies have been developed to counter these degenerative changes. Neo-proteoglycans prepared from chondroitin sulfate or hyaluronan and hyaluronan or collagen-binding peptides emulate the interactive, water imbibing, weight bearing, and surface lubricative properties of native proteoglycans. Many neo-proteoglycans outperform native proteoglycans in terms of water imbibition, matrix stabilization, and resistance to proteolytic degradation. The biospecificity of recombinant proteoglycans however, provides precise attachment to native target molecules. Visco-supplements augmented with growth factors/therapeutic cells, hyaluronan, and lubricin (orthobiologicals) have the capacity to lubricate and protect cartilage, control inflammation, and promote cartilage repair and regeneration of early cartilage lesions and may represent a more effective therapeutic approach to the treatment of mild to moderate OA and deserve further study.Similar protective perineural net structures assembled from the lectican proteoglycan family and HA also occur in the CNS/PNS. These so called perineuronal nets are visualized by immunolocalization of MAb 1B5 (+) epitope in rat brain (e) and pericellular 1B5(+) epitope expression by isolated neurons (f). Scale bars 100 µm.

show abstract

Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues

Cited by 123 publications

References 65 publications

A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Contact Info

Product

Resources

About