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

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.

[1]  Y. Henrotin,et al.  Serum Levels of Coll2-1, a Specific Biomarker of Cartilage Degradation, Are Not Affected by Sampling Conditions, Circadian Rhythm, and Seasonality. , 2019, Cartilage.

[2]  A. Mobasheri,et al.  Coll2-1 and Coll2-1NO2 as exemplars of collagen extracellular matrix turnover – biomarkers to facilitate the treatment of osteoarthritis? , 2019, Expert review of molecular diagnostics.

[3]  Ali Mobasheri,et al.  Osteoarthritis phenotypes and novel therapeutic targets. , 2019, Biochemical pharmacology.

[4]  J. Parvizi,et al.  Results of a Phase II Study to Determine the Efficacy and Safety of Genetically Engineered Allogeneic Human Chondrocytes Expressing TGF-β1 , 2019, The Journal of Knee Surgery.

[5]  M. Nevitt,et al.  Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative. , 2018, Osteoarthritis and cartilage.

[6]  C. McCulloch,et al.  Role of thigh muscle cross-sectional area and strength in progression of knee cartilage degeneration over 48 months - data from the Osteoarthritis Initiative. , 2016, Osteoarthritis and cartilage.

[7]  M. Nevitt,et al.  MRI findings associated with development of incident knee pain over 48 months: data from the osteoarthritis initiative , 2016, Skeletal Radiology.

[8]  L. Sharma,et al.  Baseline radiographic osteoarthritis and semi-quantitatively assessed meniscal damage and extrusion and cartilage damage on MRI is related to quantitatively defined cartilage thickness loss in knee osteoarthritis: the Multicenter Osteoarthritis Study. , 2015, Osteoarthritis and cartilage.

[9]  S. Majumdar,et al.  Higher Knee Flexion Moment During the Second Half of the Stance Phase of Gait Is Associated With the Progression of Osteoarthritis of the Patellofemoral Joint on Magnetic Resonance Imaging. , 2015, The Journal of orthopaedic and sports physical therapy.

[10]  F. Rannou,et al.  Early decrease of serum biomarkers of type II collagen degradation (Coll2‐1) and joint inflammation (Coll2‐1 NO2) by hyaluronic acid intra‐articular injections in patients with knee osteoarthritis: A research study part of the Biovisco study , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  M. Nevitt,et al.  Predictive validity of within-grade scoring of longitudinal changes of MRI-based cartilage morphology and bone marrow lesion assessment in the tibio-femoral joint--the MOST study. , 2012, Osteoarthritis and cartilage.

[12]  G. Baxter,et al.  Patient characteristics that predict progression of knee osteoarthritis: A systematic review of prognostic studies , 2011, Arthritis care & research.

[13]  M. Nevitt,et al.  Tibiofemoral joint osteoarthritis: risk factors for MR-depicted fast cartilage loss over a 30-month period in the multicenter osteoarthritis study. , 2009, Radiology.

[14]  R. Cancedda,et al.  Cartilage and bone extracellular matrix. , 2009, Current pharmaceutical design.

[15]  M. Nevitt,et al.  Change in MRI-detected subchondral bone marrow lesions is associated with cartilage loss: the MOST Study. A longitudinal multicentre study of knee osteoarthritis , 2008, Annals of the rheumatic diseases.

[16]  J. Reginster,et al.  New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis. , 2005, Osteoarthritis and cartilage.

[17]  H. Genant,et al.  Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. , 2004, Osteoarthritis and cartilage.

[18]  E. Roos,et al.  The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis , 2003, Health and quality of life outcomes.

[19]  M. Dougados,et al.  Outcome variables for osteoarthritis clinical trials: The OMERACT-OARSI set of responder criteria. , 2003, The Journal of rheumatology.

[20]  R. Moskowitz,et al.  Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. , 1986, Arthritis and rheumatism.

[21]  A. Mobasheri,et al.  Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes , 2019, Current opinion in rheumatology.

[22]  D’Apuzzo,et al.  Could Whole-Organ Magnetic Resonance Imaging Score ( WORMS ) Components Predict Pain in Knee Osteoarthritis ? , 2011 .