scholarly journals CIINE Reflects Collagenase-Specific CII Breakdown in Cartilage Explant and Whole Body of Canine

2013 ◽  
Vol 8 ◽  
pp. BMI.S11627 ◽  
Author(s):  
Satoko Matsukawa ◽  
Miki Tanimura ◽  
Tomoko Toyosaki-Maeda ◽  
Akihiro Noda ◽  
Mika Kobayashi ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Clinical Pathology ◽  
Type Ii Collagen ◽  
Cartilage Explants ◽  
Whole Body ◽  
Type Ii ◽  
Anterior Cruciate Ligament Transection ◽  
Cartilage Explant ◽  
Anterior Cruciate ◽  
Putative Marker

To evaluate collagenase inhibitors for the treatment of osteoarthritis and to correlate them with clinical pathology, canine cartilage explant and anterior cruciate ligament transection (ACLT) models were examined by quantifying the CII neoepitope (CIINE). This peptide is a putative marker for collagenase-specific type II collagen (CII) degradation, which is a critical step in osteoarthritis pathology. The concentration of CIINE in supernatants of canine cartilage explants showed increase upon IL-1β—stimulation and collagenase inhibitors suppressed this elevation of CIINE. In the canine ACLT model, levels of CIINE in urine (uCIINE) increased as lesions of knee joint cartilage developed and decreased in response to collagenase inhibitors. Our results suggest that CIINE reflects collagenase-specific CII degradation in canine explants and whole bodies. It is anticipated that these data will establish a tool for clarifying and bridging the efficacy and mechanism of collagenase inhibitors at the preclinical stage of drug discovery.

scholarly journals Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species

2021 ◽  
Author(s):  
Anne Gigout ◽  
Donata Harazin ◽  
Louise M. Topping ◽  
Sven Lindemann ◽  
Christian Brenneis ◽  
...  
Keyword(s):  
Collagen Type ◽  
Cruciate Ligament ◽  
Type Ii Collagen ◽  
Lateral Compartment ◽  
Cartilage Degradation ◽  
Type Ii ◽  
Early Biomarker ◽  
Cartilage Breakdown ◽  
Anterior Cruciate ◽  
Radiographic Changes

Abstract Background: Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Cartilage degradation is mostly driven by chondrocytes which produce inflammatory mediators, proteases and oxidants. Nevertheless, the early pathogenesis events are still unclear. We employed antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA. Methods: The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed at 3, 5, 7, 14 and 28 days or anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) and were sacrificed after 1, 3, 5, 7 and 14 days. Joints were stained with toluidine blue and Saffron du Gatinais for histological scoring, anti-oxPTM-CII and anti- collagen type X antibodies (anti-CX). Results: We observed oxPTM-CII staining as early as 1 or 3 days after ACLT+pMx or DMM surgeries respectively, before overt cartilage lesions were visible. It was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes and co-localized with CX staining. Both staining were weak or absent for the lateral compartment or the contralateral knees except at later timepoints. Conclusion: The results demonstrate that oxidants production and chondrocytes hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead or radiographic changes.

scholarly journals Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Anne Gigout ◽  
Donata Harazin ◽  
Louise M. Topping ◽  
Didier Merciris ◽  
Sven Lindemann ◽  
...  
Keyword(s):  
Collagen Type ◽  
Cruciate Ligament ◽  
Type Ii Collagen ◽  
Lateral Compartment ◽  
Cartilage Degradation ◽  
Type Ii ◽  
Early Biomarker ◽  
Oxidant Production ◽  
Anterior Cruciate ◽  
Radiographic Changes

Abstract Background Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Inflammatory mediators, proteases, and oxidants produced by chondrocytes are known to be responsible for driving cartilage degradation. Nevertheless, the early pathogenic events are still unclear. To investigate this, we employed an antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA. Methods The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed after 3, 5, 7, 14, and 28 days. Alternatively, anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) was performed and animals were sacrificed after 1, 3, 5, 7, and 14 days. Joints were stained with toluidine blue and saffron du Gatinais for histological scoring, anti-oxPTM-CII, and anti-collagen type X antibodies (anti-CX). Results We observed positive oxPTM-CII staining as early as 1 or 3 days after ACLT+pMx or DMM surgeries, respectively, before overt cartilage lesions were visible. oxPTM-CII was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes, and co-localized with CX staining. Staining was weak or absent for the lateral compartment or the contralateral knees except at later time points. Conclusion The results demonstrate that oxidant production and chondrocyte hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead of radiographic changes.

scholarly journals Early Detection of Osteoarthritis in the Rat With an Antibody Specific to Type II Collagen Modified by Reactive Oxygen Species

2020 ◽  
Author(s):  
Anne Gigout ◽  
Donata Harazin ◽  
Louise M. Topping ◽  
Sven Lindemann ◽  
Christian Brenneis ◽  
...  
Keyword(s):  
Collagen Type ◽  
Cruciate Ligament ◽  
Type Ii Collagen ◽  
Lateral Compartment ◽  
Cartilage Degradation ◽  
Type Ii ◽  
Early Biomarker ◽  
Cartilage Breakdown ◽  
Anterior Cruciate ◽  
Radiographic Changes

Abstract Background Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Cartilage degradation is mostly driven by chondrocytes which produce inflammatory mediators, proteases and oxidants. Nevertheless, the early pathogenesis events are still unclear. We employed antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA. Methods The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed at 3, 5, 7, 14 and 28 days or anterior cruciate ligament transection with partial meniscectomy (ACLT + pMx) and were sacrificed after 1, 3, 5, 7 and 14 days. Joints were stained with toluidine blue and Saffron du Gatinais for histological scoring, anti-oxPTM-CII and anti- collagen type X antibodies (anti-CX). Results We observed oxPTM-CII staining as early as 1 or 3 days after ACLT + pMx or DMM surgeries respectively, before overt cartilage lesions were visible. It was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes and co-localized with CX staining. Both staining were weak or absent for the lateral compartment or the contralateral knees except at later timepoints. Conclusion The results demonstrate that oxidants production and chondrocytes hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead or radiographic changes.

scholarly journals Longitudinal Analysis of Serum Biochemical Changes following Anterior Cruciate Ligament Injury and Reconstruction: A Matched Comparison-Control Analysis

2020 ◽  
Vol 8 (7_suppl6) ◽  
pp. 2325967120S0035
Author(s):  
Lara Longobardi ◽  
Hope Davis-Wilson ◽  
Brian Pietrosimone ◽  
R.Alexander Creighton ◽  
Joanne Jordan ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Time Course ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Type Ii Collagen ◽  
Metabolic Changes ◽  
Type Ii ◽  
Joint Tissue ◽  
Anterior Cruciate ◽  
Over Time

Objectives: Individuals with an anterior cruciate ligament (ACL) injury are at high risk of developing posttraumatic osteoarthritis (PTOA). A comprehensive study is needed to determine the time course of joint tissue metabolic changes occurring following ACL injury and reconstruction (ACLR). The purpose of this longitudinal nested comparison-control study was to simultaneously evaluate serum biomarkers of inflammation and cartilage matrix damage in ACL injured patients prior to ACLR and 6 and 12 months post-ACLR, as well as in matched uninjured controls. Methods: Serum was collected from 34 ACL injured individuals (53% female, 20.7±2.4 years old, 24.2±4.1 body mass index [BMI]) within 14 days of primary ACL injury (baseline), as well as at 6 and 12 months following bone-patellar-tendon-bone autograft ACLR. Serum was also collected from 34 uninjured matched controls (53% Female, 20.5±2.4 years old, 24.1±3.5 BMI) at a single timepoint. Blood was collected from the antecubital fossa, centrifuged and stored at -80°C prior to batch analysis. Commercial enzyme-linked immunosorbent assays were used to evaluate concentrations of: 1) a pro-inflammatory cytokine [Monocyte Chemoattractant Protein; MCP-1]; 2) a matrix degrading enzyme [matrix metalloproteinase-3; MMP-3]; 3) a cartilage breakdown biomarker [cartilage oligomeric matrix protein; COMP]; and type-II collagen turnover [type-II collagen cleavage: synthesis; C2C:CPII]. Separate Bonferroni-corrected independent t-tests were used to determine differences between the ACL injured group at each timepoint and uninjured controls for each biomarker (P ≤ 0.015). Similarly, separate Bonferroni-corrected dependent t-tests were used to determine differences in biomarker concentrations over time for the ACLR group. Results: Serum concentrations of MCP-1 and COMP were greater in the ACL injured individuals at all timepoints compared to the controls (P ≤ 0.015, Table 1), yet no differences were found over time in the ACL injured group. MMP-3 concentrations increased between baseline and 6 months post-ACLR (P ≤ 0.015, see Table), yet no differences were found between 6 and 12 months post-ACLR, between baseline and 12 months, or between ACLR and controls at any of the time points. C2C:CPII was not different between ACL injured individuals and controls at baseline or 6 months post-ACLR. C2C:CPII was significantly increased between 6 and 12 months-post ACLR, and was found to be greater than baseline and greater than controls at 12 months post-ACLR (P ≤ 0.015, see Table). Conclusion: Our study is critical in demonstrating the time course of multiple joint tissue metabolic changes following ACL injury and ACLR. Elevated serum MCP-1 and COMP concentrations, linked to early deleterious metabolic processes associated with PTOA development, are evident soon after ACL injury and persist at 12 months post-ACLR. Serum MMP-3 concentrations were elevated 6 months post-ACLR compared to the baseline measurements, suggesting factors occurring after ACLR initiate upregulation of matrix degrading enzymes. Furthermore, elevated C2C:CPII occurs within the first 12 months post ACLR but not until after the 6-month post-ACLR timepoint. Further studies are needed to determine how long these joint tissue metabolic changes persist after ACL injury and ACLR, as well as how joint tissue metabolism is affected by the type and timing of different surgical and nonsurgical treatments.

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