GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro

Research output: Contribution to journalJournal articleResearchpeer-review

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GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro. / Löfvall, Henrik; Katri, Anna; Dąbrowska, Aneta; Karsdal, Morten A; Luo, Yunyun; He, Yi; Manon-Jensen, Tina; Dziegiel, Morten H.; Bay-Jensen, Anne-Christine; Thudium, Christian S; Henriksen, Kim.

In: Scientific Reports, Vol. 9, No. 1, 3050, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Löfvall, H, Katri, A, Dąbrowska, A, Karsdal, MA, Luo, Y, He, Y, Manon-Jensen, T, Dziegiel, MH, Bay-Jensen, A-C, Thudium, CS & Henriksen, K 2019, 'GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro', Scientific Reports, vol. 9, no. 1, 3050. https://doi.org/10.1038/s41598-019-39803-0

APA

Löfvall, H., Katri, A., Dąbrowska, A., Karsdal, M. A., Luo, Y., He, Y., Manon-Jensen, T., Dziegiel, M. H., Bay-Jensen, A-C., Thudium, C. S., & Henriksen, K. (2019). GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro. Scientific Reports, 9(1), [3050]. https://doi.org/10.1038/s41598-019-39803-0

Vancouver

Löfvall H, Katri A, Dąbrowska A, Karsdal MA, Luo Y, He Y et al. GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro. Scientific Reports. 2019;9(1). 3050. https://doi.org/10.1038/s41598-019-39803-0

Author

Löfvall, Henrik ; Katri, Anna ; Dąbrowska, Aneta ; Karsdal, Morten A ; Luo, Yunyun ; He, Yi ; Manon-Jensen, Tina ; Dziegiel, Morten H. ; Bay-Jensen, Anne-Christine ; Thudium, Christian S ; Henriksen, Kim. / GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro. In: Scientific Reports. 2019 ; Vol. 9, No. 1.

Bibtex

@article{f281b1e44cb941a3b8aba7292c30d236,
title = "GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro",
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 GPDPLQ1237 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 GPDPLQ1237 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 GPDPLQ1237 release. Cartilage resorption-derived GPDPLQ1237 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 GPDPLQ1237 and CTX-II release were both fully inhibited by GM6001 but were not inhibited by E-64. No clinically relevant GPDPLQ1237 reactivity was identified in human serum, plasma, or urine from healthy donors or arthritis patients. In conclusion, the GPDPLQ1237 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 GPDPLQ1237 may be relevant in diseases with pathological osteoclast activity and cartilage degradation. Further studies are required to validate the neo-epitope in human samples.",
author = "Henrik L{\"o}fvall and Anna Katri and Aneta D{\c a}browska and Karsdal, {Morten A} and Yunyun Luo and Yi He and Tina Manon-Jensen and Dziegiel, {Morten H.} and Anne-Christine Bay-Jensen and Thudium, {Christian S} and Kim Henriksen",
year = "2019",
doi = "10.1038/s41598-019-39803-0",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro

AU - Löfvall, Henrik

AU - Katri, Anna

AU - Dąbrowska, Aneta

AU - Karsdal, Morten A

AU - Luo, Yunyun

AU - He, Yi

AU - Manon-Jensen, Tina

AU - Dziegiel, Morten H.

AU - Bay-Jensen, Anne-Christine

AU - Thudium, Christian S

AU - Henriksen, Kim

PY - 2019

Y1 - 2019

N2 - 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 GPDPLQ1237 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 GPDPLQ1237 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 GPDPLQ1237 release. Cartilage resorption-derived GPDPLQ1237 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 GPDPLQ1237 and CTX-II release were both fully inhibited by GM6001 but were not inhibited by E-64. No clinically relevant GPDPLQ1237 reactivity was identified in human serum, plasma, or urine from healthy donors or arthritis patients. In conclusion, the GPDPLQ1237 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 GPDPLQ1237 may be relevant in diseases with pathological osteoclast activity and cartilage degradation. Further studies are required to validate the neo-epitope in human samples.

AB - 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 GPDPLQ1237 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 GPDPLQ1237 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 GPDPLQ1237 release. Cartilage resorption-derived GPDPLQ1237 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 GPDPLQ1237 and CTX-II release were both fully inhibited by GM6001 but were not inhibited by E-64. No clinically relevant GPDPLQ1237 reactivity was identified in human serum, plasma, or urine from healthy donors or arthritis patients. In conclusion, the GPDPLQ1237 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 GPDPLQ1237 may be relevant in diseases with pathological osteoclast activity and cartilage degradation. Further studies are required to validate the neo-epitope in human samples.

U2 - 10.1038/s41598-019-39803-0

DO - 10.1038/s41598-019-39803-0

M3 - Journal article

C2 - 30816326

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 3050

ER -

ID: 215561344