Biosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthrosis

Eyre, David R.; McDevitt, C A; Billingham, M. E. J.; Muir, Helen

doi:10.1042/bj1880823

Cited by 202 publications

(150 citation statements)

References 49 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, the amount of MMP-13, as detected both as an immunoreactive protein and by the protein activity, has been found directly related to the degree of cartilage degradation determined arthroscopically (see Figure 6); in addition, a slight increase of MMP-1, related to the severity of chondromalacia, was observed, confirming previous observations [31].…”

Section: Discussionsupporting

confidence: 88%

“…Under conditions which accompany inflammatory joint disorders and changes in the composition of its extra-cellular matrix, chondrocytes undergo significant alterations which are not yet fully understood [3,[31][32][33][34]. Therefore, we focused our interest on the behavior of some molecules, such as MMPs and TIMPs, which are proposed to be active agents during joint degeneration processes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities

Marini

Fasciglione

Monteleone

et al. 2003

Clinical Biochemistry

View full text Add to dashboard Cite

Objective: A novel study has been carried out to characterize the amount and activity levels of metalloproteinases (i.e., MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13) and of their inhibitors (i.e., TIMP-1 and TIMP-2) in synovial fluid from patients (n ϭ 56) with different degrees of either chondral lesions or knee arthritis identified and classified by arthroscopy. Design and methods: Zymographies, Western blotting and ELISA tests have been used to correlate the disease stage, as determined by arthroscopy, and both the amount and the activation state of different MMPs and of their inhibitors. Results: Analysis of data obtained demonstrates that the degree of cartilage degradation, as seen by arthroscopy, is strictly related to the activity of some synovial MMPs, in particular MMP-2 and MMP-13 and on reduced inhibitory effect of MMP-2 by TIMP-2; in addition, a serine protease weighing about 125 kDa appears only in patients with severe cartilage degradation, i.e., with knee arthritis. Conclusions: On the whole, this is the first study in which an analysis of synovial MMPs/other proteinases activity and TIMPs has been strictly related to arthroscopy results in patients with different degrees of osteoarthritis. Results indicate that an imbalance between specific MMP activities and the amount of TIMPs and of its inhibitory efficiency is crucial for the disease evolution and it is related to the disease stage.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities

Marini

Fasciglione

Monteleone

et al. 2003

Clinical Biochemistry

View full text Add to dashboard Cite

show abstract

“…The increase in serum aggrecan 846, but not CPII, is more difficult to explain, because increased synthesis and gene expression of both aggrecan and type II collagen have been observed at these time points in this model, using both direct biosynthetic (33) and molecular biology (18) approaches. Moreover, the level of synovial fluid CPII is elevated in early human OA (34), although it is unclear how the stage of disease in these patients compares with that in the animals in this study.…”

Section: Body Fluid Biomarkers In Early Experimental Oa 549mentioning

confidence: 96%

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Matyas

Atley

Ionescu

et al. 2004

Arthritis & Rheumatism

141

124

View full text Add to dashboard Cite

Objective. To study 3 body fluids for changes in the levels of 5 biomarkers of cartilage metabolism during the early phases of experimental osteoarthritis (OA).Methods. Twenty skeletally mature mixed-breed canines underwent unilateral surgical transection of the anterior cruciate ligament. Samples of joint fluid, serum, and urine were obtained preoperatively and just before necropsy (3 weeks or 12 weeks postoperatively). Biomarkers included 2 markers of cartilage matrix synthesis/turnover (aggrecan 846 epitope and C-propeptide of type II collagen) and 3 markers of cartilage degradation (keratan sulfate proteoglycan epitope, the collagenase-generated cleavage epitope of type II collagen [Col2-3/4C long mono , or CIIC], and crosslinked peptides from the C-telopeptide domain of type II collagen [Col2CTx]). Significant changes in the levels of these biomarkers were determined by paired analyses.Results. Joint pathology was more severe in the 12-week group compared with the 3-week group. In joint fluid, due to limited volume, only Col2-3/4C long mono and Col2CTx were measured. Significant elevations in the levels of both of these markers were observed in experimental joints in both the 3-week group and the 12-week group. In serum, the level of aggrecan 846 epitope was elevated at both 3 weeks and 12 weeks, the level of Col2-3/4C long mono was elevated at 12 weeks, and the level of Col2CTx was elevated at both 3 weeks and 12 weeks. In urine, the level of Col2-3/4C long mono was elevated at 12 weeks after surgery.Conclusion. Levels of biomarkers of intact aggrecan proteoglycan (aggrecan 846 epitope) and type II collagen degradation (Col2-3/4C long mono and Col2CTx) were elevated early after unilateral stifle joint injury, suggesting that these markers are sensitive and specific for early cartilage changes associated with isolated joint injury in this established model of experimental OA.The early stages of osteoarthritis (OA) are difficult to diagnose. Joint structure and function are typically altered substantially before symptoms cause patients to seek medical care, that is, the osteoarthritic process begins long before OA presents as a clinical disease. The insidious onset and "silent" progression of primary OA not only obscure an early diagnosis, but also delay treatment that may help prevent further cartilage destruction and joint failure. Hence, diagnostic tests that can detect and monitor molecular events early in the pathogenesis of OA would be potentially very useful.For nearly a century, synovial fluid analysis has been important in the differential diagnosis of arthritis. Although synovial fluid analysis is useful in distinguishing between inflammatory, septic, and crystal-induced arthritis, its value in OA is limited. Similarly, routine blood and urine analyses can identify certain inflammatory arthritides and metabolic defects that cause joint pain and pathology but, as yet, reveal little about the OA process. No specific molecular markers of the OA process are currently available for clinical use, and the...

show abstract

“…The normally very slow turnover rate of cartilage matrix (1) is increased, as observed by several techniques in both animal OA models and human OA. Phasic changes in both synthesis and degradation of collagen and other matrix molecules (2)(3)(4)(5)(6) are associated with altered tissue structure and material properties (7)(8)(9).…”

mentioning

confidence: 99%

“…Such an assay indicated increased degradation of CII in a canine model of joint instability (31). However, interpretation of results from such a generic CII marker may be limited if the assay cannot distinguish between structural and newly synthesized molecules, since collagen synthesis was reported to increase after joint injury (2,10). With specificity only to degradation products of mature crosslinked CII, it should be possible to monitor the catabolic side of joint pathology more reliably.…”

mentioning

confidence: 99%

The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis

Lohmander¹,

Atley²,

Pietka³

et al. 2003

Arthritis & Rheumatism

234

165

View full text Add to dashboard Cite

Objective. To determine concentrations of crosslinked C-telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) from patients with joint injury, osteoarthritis (OA), or other knee arthritides.Methods. Two study groups were used: a crosssectional group, which included healthy-knee volunteers (reference group [REF]) and patients with pseudogout (PPA), an anterior cruciate ligament tear with or without a meniscus tear (INJ), or primary knee OA (POA); and a longitudinal group, which included patients with arthroscopic cartilage changes or septic arthritis. CTX-II was quantified by competition enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody that recognized the C-terminus of the peptide EKGPDP as a proteolytic neoepitope. Aggrecan fragments, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were determined by ELISAs.Results. Concentrations of CTX-II in SF were higher in patients with PPA, INJ, and POA than in the REF group (P < 0.001). After joint injury, mean levels of CTX-II in SF were increased above REF levels at all time intervals (P < 0.001), and were highest within hours after trauma. In those in the longitudinal study group with joint cartilage damage, variation coefficients for CTX-II were 81% (between patients) and 64% (within patient), monitored over 1 year. In a patient with septic arthritis, SF CTX-II increased at the onset of symptoms, and peaked 30-fold higher than the baseline. Concentrations of all biomarkers decreased with successful treatment.Conclusion. This is the first report to describe the release into SF of soluble molecular fragments specific for the degradation of mature, crosslinked, type II collagen (CII) in human OA and joint injury. The results provide strong evidence that the integrity of the CII network of cartilage is compromised soon after joint injury and in arthritis. This early degradation of CII may represent an important treatment target.Osteoarthritis (OA) and joint injury are characterized by remodeling and degradation of cartilage, bone, and other joint tissues. The normally very slow turnover rate of cartilage matrix (1) is increased, as observed by several techniques in both animal OA models and human OA. Phasic changes in both synthesis and degradation of collagen and other matrix molecules (2-6) are associated with altered tissue structure and material properties (7-9).Increased joint tissue turnover after injury and in OA can be detected by a release of molecules and molecular fragments into synovial fluid (SF), blood, and urine. For example, the stimulated synthesis of type II collagen (CII) results in higher levels of CII C-propeptide in SF (10,11). Stimulated aggrecan synthesis results in more aggrecan fragments carrying the 846 epitope (12). Higher synovial concentrations of matrix metalloproteinases (MMPs), such as MMP-1 and MMP-3, and proteinase activity after joint injury and in OA are consistent with the observed expression of these

show abstract

Biosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthrosis

Cited by 202 publications

References 49 publications

A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities

A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis

Contact Info

Product

Resources

About