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  • Groen, Solveig SkovlundNordic Bioscience AS,University of Copenhagen (author)

A serological type II collagen neoepitope biomarker reflects cartilage breakdown in patients with osteoarthritis

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Elsevier BV,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:485c5b61-e15d-40b2-a5a7-ceee454c3f87
  • https://lup.lub.lu.se/record/485c5b61-e15d-40b2-a5a7-ceee454c3f87URI
  • https://doi.org/10.1016/j.ocarto.2021.100207DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Objectives: There is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker. Methods: A type II collagen specific neoepitope (T2CM) was identified by mass spectrometry and monoclonal antibodies were raised towards the epitope, employed in a chemiluminescence immunoassay. T2CM was assessed in bovine cartilage explants with or without MMP-13 inhibitor, and explant supernatants were analyzed by Western blot. T2CM was measured in plasma samples from one study (n ​= ​48 patients) where OA patients were referred to total knee replacement (TKR). Additionally, T2CM was quantified in serum from OA patients receiving salmon calcitonin treatment (sCT) (n ​= ​50) compared to placebo (n ​= ​57). Results: The T2CM assay was technically robust (13/4 ​% inter/intra-variation) and specific for the type II collagen fragment cleaved by MMP-1 and -13. The MMP-13 inhibitor reduced the T2CM release from bovine cartilage explants receiving catabolic treatment. These results were confirmed by Western blot. In human end-stage OA patients (scheduled for TKR), the T2CM levels were elevated compared to moderate OA (p<0.004). The OA patients receiving sCT had lower levels of T2CM compared to placebo group after 1, 6, and 24 months of treatment (p ​= ​0.0285, p ​= ​0.0484, p ​= ​0.0035). Conclusions: To our knowledge, T2CM is the first technically robust serological biomarker assay which has shown biological relevance in ex vivo models and OA cohorts. This suggests that T2CM may have potential as a translational biomarker for cartilage degradation.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Sinkeviciute, DovileLund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Molekylär skelettbiologi,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Molecular Skeletal Biology,Lund University Research Groups,Nordic Bioscience AS(Swepub:lu)do6165si (author)
  • Bay-Jensen, Anne ChristineNordic Bioscience AS (author)
  • Thudium, Christian S.Nordic Bioscience AS(Swepub:lu)med-ctu (author)
  • Karsdal, Morten A.Nordic Bioscience AS (author)
  • Thomsen, Simon FrancisBispebjerg Hospital (author)
  • Lindemann, SvenMerck KGaA (author)
  • Werkmann, DanielaMerck KGaA (author)
  • Blair, JosephNordic Bioscience AS (author)
  • Staunstrup, Line MærskNordic Bioscience AS (author)
  • Önnerfjord, PatrikLund University,Lunds universitet,Molekylär skelettbiologi,Forskargrupper vid Lunds universitet,Molecular Skeletal Biology,Lund University Research Groups(Swepub:lu)akem-pon (author)
  • Arendt-Nielsen, LarsAalborg University (author)
  • Nielsen, Signe HolmTechnical University of Denmark,Nordic Bioscience AS (author)
  • Nordic Bioscience ASUniversity of Copenhagen (creator_code:org_t)

Related titles

  • In:Osteoarthritis and Cartilage Open: Elsevier BV3:42665-9131

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