scholarly journals FRI0405 CARTILAGE BIOMARKERS S-COLL2-1 AND S-COLL2-1NO2 ARE HELPFUL IN IDENTIFYING KNEE OSTEOARTHRITIS PATIENTS AT RISK OF DISEASE WORSENING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 801.2-801
Author(s):  
Y. Henrotin ◽  
B. Costes ◽  
M. Malaise ◽  
D. Loeuille ◽  
T. Conrozier ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Structural Features ◽  
Type Ii ◽  
Knee Oa ◽  
Link Type ◽  
Patients At Risk ◽  
One Year ◽  
Medial Femorotibial Joint ◽  
Femorotibial Joint

Background:Coll2-1 is a peptide of 9 amino acid located in the triple helix of type II collagen molecule reflecting cartilage degradation (1). Coll2-1NO2 is the nitrated form of Coll2-1 and considered as a biomarker of the inflammatory-related cartilage degradation (2). This peptide is involved in osteoarthritis physiopathology since it was demonstrated that Coll2-1 induced synovitis in rat.Objectives:To identify if biochemical markers s-Coll2-1 and s-Coll2-1NO2 are associated to knee osteoarthritis (OA), focusing on pain, function as well as structural features assessed by MRI in various knee compartments and to assess their ability at predicting knee OA worsening.Methods:116 subjects with knee OA were followed during one year with pain, function and MRI evaluation (PRODIGE study,NCT02070224). Type II collagen-specific biomarker Coll2-1 and its nitrated form Coll2-1NO2 were directly measured in serum using immunoassays at baseline and after three, six and twelve months follow-up.Results:sColl2-1 and sColl2-1NO2 were associated to several baseline knee features quantified with Whole-Organ Magnetic Resonance Imaging Score (WORMS). S-Coll2-1 was significantly correlated with bursitis (r=0.29, P<0.01), bone attrition (r=0.25, P=0.01), cysts (r=0.24, P=0.02) and cartilage (r=0.23, P=0.03) WORMS sub-scores for the whole joint as well as with the medial femorotibial joint sum score (r=0.26, P=0.01) and medial femorotibial joint cartilage (r=0.23, P=0.02). s-Coll2-1NO2 was correlated with WORMS total score (r=0.23, P=0.02), WORMS scores in the patellofemoral (r=0.23, P=0.02) and medial femorotibial compartments (r=0.21, P=0.03) and with osteophytes scores (r=0.27, P<0.01). Baseline s-Coll2-1NO2 was higher in subjects with a pain worsening (426.4 pg/mL [278.04-566.95]) as compared to non-progressors (306.84 [200.37-427.84]) over one year (AUC=0.655, P=0.015).Conclusion:Cartilage biomarkers s-Coll2-1 and s-Coll2-1NO2 are associated to several knee OA features quantified with WORMS scoring system on MRI. Serum values of Coll2-1NO2 are also associated to a worsening of target knee pain over one year. Coll2-1 and Coll2-1NO2, in association with other structural features, pain and function, could help at identifying OA phenotypes and patients at risk of OA worsening.References:[1]Mobasheri A, Lambert C, Henrotin Y. Coll2-1 and Coll2-1NO2 as exemplars of collagen extracellular matrix turnover - biomarkers to facilitate the treatment of osteoarthritis? Expert Rev Mol Diagn. 2019 Sep;19(9):803-812. doi: 10.1080/14737159.2019.1646641. Epub 2019 Sep 4.[2]Lambert C, Borderie D, Dubuc JE, Rannou F, Henrotin Y. Type II collagen peptide Coll2-1 is an actor of synovitis. Osteoarthritis Cartilage. 2019 Nov;27(11):1680-1691. doi: 10.1016/j.joca.2019.07.009. Epub 2019 Jul 17.Acknowledgments:PRODIGE study (NCT02070224) was performed in the framework of a convention between the Walloon region and ARTIALIS SA. (convention n°6905).Disclosure of Interests:Yves Henrotin Grant/research support from: HEEL, TILMAN, Berenice Costes Employee of: Artialis SA, Michel Malaise: None declared, Damien Loeuille: None declared, Thierry Conrozier Consultant of: LABRHA, SANOFI, MEDAC, Yves Maugars: None declared, Franz Pelousse Shareholder of: Sodiray, Jean-Marc Lemaire Shareholder of: Sodiray, Thibault Helleputte Shareholder of: DNAlytics, Cedric Tits Employee of: DNAlytics, Elisabeth Cobraiville Employee of: Artialis SA, Sebastien Pirson Employee of: Artialis, Laetitia Garcia Employee of: Artialis, Alain Labasse Employee of: Artialis SA, Anne-Christine Hick Employee of: Artialis SA

Cartilage Biomarkers Coll2-1 and Coll2-1NO2 Are Associated with Knee OA MRI Features and Are Helpful in Identifying Patients at Risk of Disease Worsening

Cartilage ◽  
2021 ◽  
pp. 194760352110218
Author(s):  
Anne-Christine Hick ◽  
Michel Malaise ◽  
Damien Loeuille ◽  
Thierry Conrozier ◽  
Yves Maugars ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Type Ii Collagen ◽  
Resonance Imaging ◽  
Cross Sectional ◽  
Knee Oa ◽  
Mri Features ◽  
Medial Femorotibial Joint ◽  
Femorotibial Joint ◽  
Cartilage Biomarkers

Objective: To assess the cross-sectional association between serum levels of Coll2-1 and Coll2-1NO2, two cartilage degradation biomarkers; the burden of magnetic resonance imaging (MRI) features and clinical outcomes; and to evaluate the predictive value of these biomarkers on progression. Design: A total of 121 subjects with knee osteoarthritis (OA) were followed during 1 year with pain, function, and MRI assessment (PRODIGE study). Type II collagen-specific biomarker Coll2-1 and its nitrated form Coll2-1NO2 were directly measured in serum using immunoassays at baseline and after 3-, 6-, and 12-month follow-up. Results: Serum Coll2-1 and Coll2-1NO2 were correlated with several baseline knee features quantified with Whole-Organ Magnetic Resonance Imaging Score (WORMS). Coll2-1 was significantly correlated with periarticular cysts/bursitis (ρ = 0.29, P < 0.01), subarticular bone attrition (ρ = 0.25, P = 0.01), subarticular cysts (ρ = 0.24, P = 0.02), and articular cartilage integrity (ρ = 0.23, P = 0.03) WORMS subscores for the whole joint as well as with the medial femorotibial joint sum score (ρ = 0.26, P = 0.01) and medial femorotibial joint cartilage (ρ = 0.23, P = 0.02). Coll2-1NO2 correlated with WORMS total score (ρ = 0.23, P = 0.02), WORMS scores in the patellofemoral (ρ = 0.23, P = 0.02) and medial femorotibial compartments (ρ = 0.21, P = 0.03), with osteophytes scores (ρ = 0.27, P < 0.01), subarticular cysts (ρ = 0.24, P = 0.019), and intraarticular loose bodies (ρ = 0.27, P = 0.007). Baseline Coll2-1NO2 was higher in subjects with a pain worsening (426.4 pg/mL [278.04-566.95]) as compared to non-progressors (306.84 pg/mL [200.37-427.84]) over 1 year (AUC = 0.655, P = 0.015). Conclusion: Serum cartilage biomarkers Coll2-1 and Coll2-1NO2 are associated with several knee OA features quantified with WORMS. Our study also shows that the baseline value of Coll2-1NO2 is positively associated with pain worsening.

scholarly journals One-year increase of Coll 2-1, a new marker of type II collagen degradation, in urine is highly predictive of radiological OA progression

2005 ◽  
Vol 13 (12) ◽  
pp. 1059-1065 ◽  
Author(s):  
M.A. Deberg ◽  
A.H. Labasse ◽  
J. Collette ◽  
L. Seidel ◽  
J.-Y. Reginster ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Collagen Degradation ◽  
Type Ii ◽  
One Year

scholarly journals Reduction of Matrix Metallopeptidase 13 and Promotion of Chondrogenesis by Zeel T in Primary Human Osteoarthritic Chondrocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Christelle Sanchez ◽  
Kathrin Hemmer ◽  
Natascha Krömmelbein ◽  
Bernd Seilheimer ◽  
Jean-Emile Dubuc ◽  
...  
Keyword(s):  
Differential Expression Analysis ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Alginate Beads ◽  
Protein Quantification ◽  
Type Ii ◽  
Osteoarthritic Chondrocytes ◽  
Matrix Metallopeptidase ◽  
Oa Chondrocytes

Objectives: Zeel T (Ze14) is a multicomponent medicinal product. Initial preclinical data suggested a preventive effect on cartilage degradation. Clinical observational studies demonstrated that Ze14 reduced symptoms of osteoarthritis (OA), including stiffness and pain. This study aimed to explore these effects further to better understand the mode of action of Ze14 on human OA chondrocytes in vitro.Methods: Primary chondrocytes were obtained from the knees of 19 OA patients and cultured either as monolayers or in alginate beads. The cultures were treated with 20% or 10% (v/v) Ze14 or placebo. For RNA-seq, reads were generated with Illumina NextSeq5000 sequencer and aligned to the human reference genome (UCSC hg19). Differential expression analysis between Ze14 and placebo was performed in R using the DESeq2 package. Protein quantification by ELISA was performed on selected genes from the culture medium and/or the cellular fractions of primary human OA chondrocyte cultures.Results: In monolayer cultures, Ze14 20% (v/v) significantly modified the expression of 13 genes in OA chondrocytes by at least 10% with an adjusted p-value &lt; 0.05: EGR1, FOS, NR4A1, DUSP1, ZFP36, ZFP36L1, NFKBIZ, and CCN1 were upregulated and ATF7IP, TXNIP, DEPP1, CLEC3A, and MMP13 were downregulated after 24 h Ze14 treatment. Ze14 significantly increased (mean 2.3-fold after 24 h, p = 0.0444 and 72 h, p = 0.0239) the CCN1 protein production in human OA chondrocytes. After 72 h, Ze14 significantly increased type II collagen pro-peptide production by mean 27% (p = 0.0147). For both time points CCN1 production by OA chondrocytes was correlated with aggrecan (r = 0.66, p = 0.0004) and type II collagen pro-peptide (r = 0.64, p = 0.0008) production. In alginate beads cultures, pro-MMP-13 was decreased by Ze14 from day 7–14 (from −16 to −25%, p &lt; 0.05) and from day 17–21 (−22%, p = 0.0331) in comparison to controls.Conclusion: Ze14 significantly modified the expression of DUSP1, DEPP1, ZFP36/ZFP36L1, and CLEC3A, which may reduce MMP13 expression and activation. Protein analysis confirmed that Ze14 significantly reduced the production of pro-MMP-13. As MMP-13 is involved in type II collagen degradation, Ze14 may limit cartilage degradation. Ze14 also promoted extracellular matrix formation arguably through CCN1 production, a growth factor well correlated with type II collagen and aggrecan production.

Serum Levels of Coll2-1, a Specific Biomarker of Cartilage Degradation, Are Not Affected by Sampling Conditions, Circadian Rhythm, and Seasonality

Cartilage ◽  
2019 ◽  
pp. 194760351987848 ◽  
Author(s):  
Anne-Christine Hick ◽  
Misch Fonck ◽  
Bérénice Costes ◽  
Elisabeth Cobraiville ◽  
Sébastien Pirson ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Healthy Subjects ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Cartilage Degradation ◽  
Blood Collection ◽  
Knee Oa ◽  
Significant Difference ◽  
Collection Tube ◽  
Study Type

Objective: To assess intraindividual biological variability of serum cartilage specific biomarker Coll2-1 and define the best standardized conditions for blood sampling. Design: Blood samples were taken from 116 subjects with knee osteoarthritis (OA) at a single time point (PRODIGE study) and from 15 healthy subjects under various conditions, including fasting condition, sampling time and season, blood treatment, and type of blood collection tube (COVAR study). Type II collagen-specific biomarker Coll2-1 was directly measured in serum using an immunoassay. Results: There was no significant difference on Coll2-1 values between samples collected at any of the 5 sampling times or at any of the sampling days measured. None of the sampling parameters tested had a significant impact on Coll2-1 value (clotting time, clotting temperature and temperature of blood centrifugation, type of tube). On the contrary, differences were found in between subjects and between subjects with knee OA and healthy subjects. Conclusion: Coll2-1 measurement is not affected by sampling specific conditions, circadian rhythm or seasons but was found elevated in subject with knee OA indicating that Coll2-1 serum variation is not linked to the study environment, but to cartilage degradation in OA. Coll2-1 assay is sufficiently robust for use in OA clinical trials.

A new biochemical marker of cartilage degradation: Measurement of Mmp-Derived Type II collagen fragments in human urine

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S72
Author(s):  
J. Wang ◽  
I. Byrjalsen ◽  
Q. Liu ◽  
Q. Zheng ◽  
M.A. Karsdal ◽  
...  
Keyword(s):  
Human Urine ◽  
Biochemical Marker ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Type Ii ◽  
Degradation Measurement

scholarly journals Norepinephrine Inhibits Synovial Adipose Stem Cell Chondrogenesis via α2a-Adrenoceptor-Mediated ERK1/2 Activation

2019 ◽  
Vol 20 (13) ◽  
pp. 3127 ◽  
Author(s):  
Karima El Bagdadi ◽  
Frank Zaucke ◽  
Andrea Meurer ◽  
Rainer H. Straub ◽  
Zsuzsa Jenei-Lanzl
Keyword(s):  
Stem Cells ◽  
Type Ii Collagen ◽  
Collagen Content ◽  
Type Ii ◽  
Adipose Stem Cell ◽  
Future Studies ◽  
Knee Oa ◽  
Sulfated Glycosaminoglycan ◽  
Resident Stem Cells

In recent years, first evidences emerged that sympathetic neurotransmitters influence osteoarthritis (OA) manifestation. Joint-resident stem cells might contribute to cartilage repair, however, their chondrogenic function is reduced. The neurotransmitter norepinephrine (NE) was detected in the synovial fluid of trauma and OA patients. Therefore, the aim of this study was to analyse how NE influences the chondrogenesis of synovial adipose tissue-derived stem cells (sASCs). sASCs were isolated from knee-OA patients synovia. After adrenoceptor (AR) expression analysis, proliferation and chondrogenic differentiation in presence of NE and/or α- and β-AR antagonist were investigated. Cell count, viability, chondrogenic and hypertophic gene expression, sulfated glycosaminoglycan (sGAG) and type II collagen content were determined. Key AR-dependent signaling (ERK1/2, PKA) was analyzed via western blot. sASC expressed α1A-, α1B-, α2A-, α2B-, α2C-, and β2-AR in monolayer and pellet culture. NE did not affect proliferation and viability, but 10−7 and 10−6 M NE significantly reduced sGAG and type II collagen content as well as ERK1/2 phosphorylation. These effects were fully reversed by yohimbine (α2-AR antagonist). Our study confirms the important role of NE in sASC chondrogenic function and provides new insights in OA pathophysiology. Future studies might help to develop novel therapeutic options targeting neuroendocrine pathways for OA treatment.

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