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GPDPLQ 1237 -A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro.
- Source :
-
Scientific reports [Sci Rep] 2019 Feb 28; Vol. 9 (1), pp. 3050. Date of Electronic Publication: 2019 Feb 28. - Publication Year :
- 2019
-
Abstract
- C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe the GPDPLQ <subscript>1237</subscript> ELISA which targets the EKGPDPLQ↓ neo-epitope, an elongated version of the CTX-II neo-epitope (EKGPDP↓), speculated to be a blood-precursor of CTX-II generated by the cysteine protease cathepsin K. Human osteoclast cartilage resorption cultures as well as oncostatin M and tumour necrosis factor α-stimulated bovine cartilage explant cultures were used to validate GPDPLQ <subscript>1237</subscript> biologically by treating the cultures with the cysteine protease inhibitor E-64 and/or the matrix metalloproteinase (MMP) inhibitor GM6001 to assess the potential contributions of these two protease classes to GPDPLQ <subscript>1237</subscript> release. Cartilage resorption-derived GPDPLQ <subscript>1237</subscript> release was inhibited by E-64 (72.1% inhibition), GM6001 (75.5%), and E-64/GM6001 (91.5%), whereas CTX-II release was inhibited by GM6001 (87.0%) but not by E-64 (5.5%). Cartilage explant GPDPLQ <subscript>1237</subscript> and CTX-II release were both fully inhibited by GM6001 but were not inhibited by E-64. No clinically relevant GPDPLQ <subscript>1237</subscript> reactivity was identified in human serum, plasma, or urine from healthy donors or arthritis patients. In conclusion, the GPDPLQ <subscript>1237</subscript> biomarker is released during osteoclast-derived cysteine protease- and MMP-mediated cartilage degradation in vitro, whereas CTX-II release is mediated by MMPs and not by cysteine proteases, as well as from MMP-mediated cartilage degradation under a pro-inflammatory stimulus. These findings suggest that GPDPLQ <subscript>1237</subscript> may be relevant in diseases with pathological osteoclast activity and cartilage degradation. Further studies are required to validate the neo-epitope in human samples.
- Subjects :
- Animals
Arthritis, Experimental immunology
Arthritis, Experimental pathology
Cartilage, Articular drug effects
Cartilage, Articular immunology
Cattle
Collagen Type II immunology
Cysteine Proteases metabolism
Cysteine Proteinase Inhibitors pharmacology
Dipeptides pharmacology
Enzyme-Linked Immunosorbent Assay
Freund's Adjuvant administration & dosage
Freund's Adjuvant immunology
Humans
Limit of Detection
Matrix Metalloproteinase Inhibitors pharmacology
Matrix Metalloproteinases metabolism
Mice
Osteoclasts drug effects
Osteoclasts immunology
Peptide Fragments immunology
Rats
Synovial Fluid immunology
Synovial Fluid metabolism
Arthritis, Experimental diagnosis
Cartilage, Articular pathology
Collagen Type II analysis
Epitopes immunology
Osteoclasts metabolism
Peptide Fragments analysis
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 30816326
- Full Text :
- https://doi.org/10.1038/s41598-019-39803-0