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Extracellular Matrix Research, Hepatic System, Non-Alcoholic Fatty Liver Disease
9. Apr 2020

Collagen Biology and Non-Invasive Biomarkers of Liver Fibrosis

There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv…

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Gastrointestinal, Extracellular Matrix Research
3. Apr 2020

A Fragment of Collagen Type VI alpha-3 Chain Is Elevated in Serum From Patients With Gastrointestinal Disorders

Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring…

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Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
9. Mar 2020

Increased Von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated With Emphysema, Exacerbations and Elevated Mortality Risk

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,…

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Hepatic System, Non-Alcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease
6. Jan 2020

Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti…

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Hepatic System, Extracellular Matrix Research, Biomarker position
28. Dec 2019

Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition.

An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify …

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Authors:

  • Mazza G,
  • Telese A,
  • Al-Akkad W,
  • Frenguelli L,
  • Levi A,
  • Marrali M,
  • Longato L,
  • Thanapirom K,
  • Vilia MG,
  • Lombardi B,
  • Crowley C,
  • Crawford M,
  • Karsdal MA,
  • Leeming DJ,
  • Marrone G,
  • Bottcher K,
  • Robinson B,
  • Del Rio Hernandez A,
  • Tamburrino D,
  • Spoletini G,
  • Malago M,
  • Hall AR,
  • Godovac-Zimmermann J,
  • Luong TV,
  • De Coppi P,
  • Pinzani M,
  • Rombouts K,
Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
2. Dec 2019

End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort.

BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized tha…

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Hepatic System
25. Oct 2019

A Phase 1 Trial of Autologous Macrophage Therapy for Liver Cirrhosis

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups…

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Authors:

  • Moroni F,
  • Dwyer BJ,
  • Graham C,
  • Pass C,
  • Bailey L,
  • Ritchie L,
  • Mitchell D,
  • Glover A,
  • Lauire A,
  • Doig S,
  • Hargreaves E,
  • Fraser AR,
  • Turner ML,
  • Cambpell JDM,
  • McGowan NWA,
  • Barry J,
  • Moore JK,
  • Hayes PC,
  • Leeming DJ,
  • Nielsen MJ,
  • Musa K,
  • Fallowfield JA,
  • Forbes SJ,
Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Oct 2019

Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program.

BACKGROUND:
Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes.

AIMS:
To evaluate the effects of a short, web-based, individualised exercise prog…

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Authors:

  • Huber Y,
  • Pfirrmann D,
  • Gebhardt I,
  • Labenz C,
  • Gehrke N,
  • Straub C,
  • Ruckes C,
  • Bantel H,
  • Belda E,
  • Clément K,
  • Leeming DJ,
  • Karsdal MA,
  • Galle PR,
  • Simon P,
  • Schattenberg JM,
Hepatic System, Biomarker position
16. Oct 2019

Serum markers of type III and IV procollagen processing predict recurrence of fibrosis in liver transplanted patients.

Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were…

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Respiratory System, Biomarker position, Extracellular Matrix Research, Idiopathic Pulmonary Fibrosis
12. Jul 2019

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was ass…

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Authors:

  • Orlan LA,
  • Duggan AR,
  • Oballa E,
  • Taggart SC,
  • Simpson JK,
  • Kang'ombe AR,
  • Braybrooke R,
  • Molyneaux PL,
  • North B,
  • Karkera Y,
  • Leeming DJ,
  • Karsdal MA,
  • Nanthakumar CB,
  • Fahy WA,
  • Marshall RP,
  • Jenkins RG,
  • Maher TM,
Hepatic System, Extracellular Matrix Research
11. Jul 2019

Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART

Abstract
Background and aims
Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recen…

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Authors:

  • Dold L,
  • Nielsen MJ,
  • Praktiknjo M,
  • Schwarzer-Zander C,
  • Boesecke C,
  • Schierwagen R,
  • Mohr R,
  • Wasmuth JC,
  • Jansen C,
  • Bischoff J,
  • Rockstroh J,
  • Karsdal MA,
  • Trebicka J,
  • Leeming DJ,
Hepatic System, Endocrinology, Type 2-Diabetes
1. Jul 2019

Use of Plasma Fragments of Propeptides of Type III, V, and VI Procollagen for the Detection of Liver Fibrosis in Type 2 Diabetes

OBJECTIVE:
This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS:
Patients with T2DM (n = 191) underwent a…

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Respiratory System, Chronic Obstructive Pulmonary Disease
9. Mar 2019

Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort

Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es…

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Hepatic System, Non-Alcoholic Steatohepatitis
1. Mar 2019

Biochemical and histological characterisation of an experimental rodent model of non-alcoholic steatohepatitis - Effects of a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist and a glucagon-like peptide-1 analogue

BACKGROUND:
Non-alcoholic steatohepatitis (NASH) is a prevalent disease that is highly associated with the metabolic syndrome and type II diabetes. The development of in vivo models that reflect all nuances of the human NASH pathology is essential for drug discovery and development. We aimed to fur…

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Hepatic System, Gastrointestinal
12. Feb 2019

Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis

OBJECTIVES:
Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assesse…

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Extracellular Matrix Research, Respiratory System, Idiopathic Pulmonary Fibrosis, Lung, Chronic Obstructive Pulmonary Disease
12. Feb 2019

Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders

OBJECTIVES:
Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which …

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Hepatic System, Extracellular Matrix Research, Renal System
9. Feb 2019

Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis

BACKGROUND & AIMS:
Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced …

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Authors:

  • Lehmann J,
  • Praktiknjo M,
  • Nielsen MJ,
  • Schierwagen R,
  • Meyer C,
  • Thomas D,
  • Violi F,
  • Strassburg CP,
  • Bendtsen F,
  • Møller S,
  • Krag A,
  • Karsdal M,
  • Leeming DJ,
  • Trebicka J,
Respiratory System, Idiopathic Pulmonary Fibrosis, Oncology, Lung
30. Nov 2018

A serological marker of the N-terminal neoepitope generated during LOXL2 maturation is elevated in patients with cancer or idiopathic pulmonary fibrosis

OBJECTIVES:
Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation.

DESI…

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Cardiovascular System, Atherosclerosis
6. Nov 2018

Markers of Basement Membrane Remodeling Are Associated With Higher Mortality in Patients With Known Atherosclerosis.

Background Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be assoc…

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Respiratory System, Chronic Obstructive Pulmonary Disease
1. Oct 2018

Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease.

BACKGROUND:
The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of t…

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Authors:

  • Schuppan D,
  • Leeming DJ,
  • papakonstantinou E,
  • Kostikas K,
  • Boersma W,
  • Louis R,
  • Milenkovik B,
  • Aerts J,
  • Sand JM,
  • Wouters EFM,
  • Rohde G,
  • Prat C,
  • Torres A,
  • Welte T,
  • Tamm M,
  • Karsdal M,
  • Stolz D,
Chronic Obstructive Pulmonary Disease, Respiratory System
10. Sep 2018

Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…

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Respiratory System, Chronic Obstructive Pulmonary Disease
10. Sep 2018

Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…

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Hepatic System
5. Sep 2018

No effect of rifaximin on soluble CD163, mannose receptor of type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized placebo controlled trial

BACKGROUND AND AIMS:
Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sy…

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Hepatic System
5. Sep 2018

No effect of rifaximin on soluble CD163, mannose receptor or type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized, placebo controlled trial.

BACKGROUND AND AIMS:
Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sy…

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Hepatic System, Hepatitis B/C
3. Sep 2018

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND:
Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with…

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Authors:

  • El Sharkawy R,
  • Thabet K,
  • Lampertico P,
  • Petta S,
  • Mangia A,
  • Berg T,
  • Netwally M,
  • Bayoumi A,
  • Boonstra A,
  • Brouwer WP,
  • Smedile A,
  • Abate ML,
  • Loglio A,
  • Douglas MW,
  • Khan A,
  • Santoro R,
  • Fischer J,
  • Leeming DJ,
  • Liddle C,
  • George J,
  • Eslam M,
Hepatic System
30. Aug 2018

Assessment of liver fibrosis progresion and regression by a serological collagen turnover profile

OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…

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Hepatitis B/C, Hepatic System
30. Aug 2018

Assessment of Liver Fibrosis Progression and Regression by a Serological Collagen Turnover Profile.

OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…

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Cardiovascular System, Atherosclerosis, Extracellular Matrix Research, Biomarker position
28. Aug 2018

A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis.

OBJECTIVE:
Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explor…

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Lung, Respiratory System, Oncology
1. Aug 2018

A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer - implications of a new collagen chaperone function of SPARC

The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance…

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Oncology, Colorectal, Gastrointestinal, Inflammatory Bowel Disease
20. Jul 2018

Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders

Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have bioma…

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Hepatic System
16. Jul 2018

Serological markers of extracellular matrix remodeling predict transplant-free survival in primary sclerosing cholangitis

BACKGROUND:
Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established.

AIM:
To evaluate the prognostic utility of four biomarkers of…

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Authors:

  • Nielsen MJ,
  • Thorburn D,
  • Leeming DJ,
  • Hov JR,
  • Nygård S,
  • Moum B,
  • Saffioti F,
  • Gilja OH,
  • Boberg KM,
  • Mazza G,
  • Røsjø H,
  • Pinzani M,
  • Karlsen TH,
  • Karsdal MA,
  • Vesterhus M,
Non-Alcoholic Fatty Liver Disease, Hepatic System
16. Jul 2018

ADAPT: An algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis.

BACKGROUND AND AIM:
Given the high global prevalence of non-alcoholic fatty liver disease (NAFLD), the need for relevant non-invasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis (≥F3) is the most crucial, …

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Authors:

  • Daniels SJ,
  • Leeming DJ,
  • Eslam M,
  • Hashem AM,
  • Nielsen MJ,
  • Krag A,
  • Karsdal MA,
  • Grove JI,
  • Guha IN,
  • Kawaguchi T,
  • Torimura T,
  • McLeod D,
  • Akiba J,
  • Kaye P,
  • de Boer B,
  • Aithal GP,
  • Adams LA,
  • George J,
Oncology, Breast
20. Jun 2018

High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts.

Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two i…

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Authors:

  • Lipton A,
  • Leitzel K,
  • Polimera HV,
  • Ali SM,
  • Naggabhairu V,
  • Marks E,
  • Richardson AE,
  • Krecko L,
  • Ali A,
  • Koestler W,
  • Esteva FJ,
  • Leeming DJ,
  • Karsdal MA,
  • Willumsen N,
Respiratory System, Extracellular Matrix Research
4. May 2018

A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia

BACKGROUND:
Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exa…

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Authors:

  • Sand JMB,
  • Tanino Y,
  • Karsdal MA,
  • Nikaido T,
  • Misa K,
  • Sato Y,
  • Togawa R,
  • Wang X,
  • Leeming DJ,
  • Munakata M,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
25. Apr 2018

Aggrecanase degradation of type III collagen is associated with clinical knee pain

There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collag…

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Extracellular Matrix Research
13. Apr 2018

Mass spectrometry-based identification of cross-links in proteins exposed to photo-oxidation and peroxyl radicals using 18/O labeling and optimized MS/MS fragmentation

Protein cross-links are formed in regulated biochemical processes in many biological systems, but they are also generated inadvertently via the reactions of exogenous or endogenous oxidants. Site-specific identification and characterization of such cross-links is challenging and the goal was therefo…

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Authors:

  • Mariotti M,
  • Leinisch F,
  • Leeming DJ,
  • Svensson B,
  • Davies MJ,
  • Hägglund P,
Extracellular Matrix Research, Systemic Sclerosis, Rheumatology, Chronic Obstructive Pulmonary Disease
1. Mar 2018

Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders

Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi…

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Hepatic System
18. Jan 2018

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Patients with end-stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute-on-chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III pl…

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Journal:

Authors:

  • Praktiknjo M,
  • Lehmann J,
  • Nielsen MJ,
  • Schierwagen R,
  • Uschner FE,
  • Meyer C,
  • Thomas D,
  • Strassburg CP,
  • Bendtsen F,
  • Møller S,
  • Krag A,
  • Karsdal MA,
  • Leeming DJ,
  • Trebicka J,
Chronic Obstructive Pulmonary Disease, Respiratory System
4. Dec 2017

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

BACKGROUND:
Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.

METHODS:
One thousand COPD subjects from the observatio…

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Authors:

  • Leeming DJ,
  • Byrjalsen I,
  • Sand JMB,
  • Bihlet AR,
  • Lange P,
  • Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators,
  • Thal-Singer R,
  • Miller BE,
  • Karsdal MA,
  • Vestbo J,
Gastrointestinal, Hepatitis B/C, Hepatic System
25. Oct 2017

PRO-C3: a new and more precise collagen marker for liver fibrosis in patients with chronic hepatitis C

OBJECTIVE:
Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) both …

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Authors:

  • Hansen JF,
  • Juul Nielsen M,
  • Nyström K,
  • Leeming DJ,
  • Lagging M,
  • Norkrans G,
  • Brehm Christensen P,
  • Karsdal MA,
Oncology, Lung
9. Aug 2017

Cathepsin-S degraded decorin are elevated in fibrotic lung disorders - development and biological validation of a new serum biomarker

BACKGROUND:
Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue h…

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Extracellular Matrix Research
21. Jul 2017

The good and the bad collagens of fibrosis - Their role in signaling and organ function

Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or…

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Cardiovascular System, Type 2-Diabetes
17. Jul 2017

Is cardiovascular disease in patients with diabetes associated with serum levels of MMP-2, LOX, and the elastin degradation products ELM and ELM-2?

BACKGROUND:
Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in …

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Oncology, Colorectal
13. May 2017

Unique insight into microenvironmental changes in colorectal cancer: Ex vivo assessment of matrix metalloprotease-mediated molecular changes in human colorectal tumor tissue and corresponding non-neoplastic adjacent tissue

Matrix metalloprotease (MMP)-mediated tissue remodeling is one of the malignant changes driving colorectal cancer. Measurement of altered MMP expression/activity is not sufficient to fully understand the effect of MMP-mediated tissue remodeling. Biomarkers are required that specifically reflect the …

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Lung
7. Mar 2017

Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non-Small Cell Lung Cancer

Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential …

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Extracellular Matrix Research, Biomarker position, Oncology
11. Feb 2017

Excessive matrix metalloprotease-mediated degradation of interstitial tissue (type I collagen) independently predicts short-term survival in an observational study of postmenopausal women diagnosed with cancer

Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predict…

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Extracellular Matrix Research
19. Jan 2017

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elas…

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Hepatic System, Type 2-Diabetes
20. Oct 2016

Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy

There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…

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Extracellular Matrix Research, Respiratory System
4. Oct 2016

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study

BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…

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Hepatic System, Hepatitis B/C, Extracellular Matrix Research
3. Oct 2016

Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury

BACKGROUND:
While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical.
…

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Type 2-Diabetes
8. Sep 2016

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…

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Respiratory System, Chronic Obstructive Pulmonary Disease
7. Sep 2016

Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease

OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been…

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Chronic Obstructive Pulmonary Disease
26. Aug 2016

Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD

BACKGROUND:
Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.

METHODS…

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Extracellular Matrix Research
1. Aug 2016

Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

OBJECTIVES:
Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competiti…

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Colorectal
28. Jul 2016

Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients

During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of prote…

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Extracellular Matrix Research
27. Jul 2016

Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeling

Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the E…

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Oncology
13. Jul 2016

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

BACKGROUND:
An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded t…

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Hepatitis B/C, Hepatic System
25. Sep 2015

Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

BACKGROUND AND AIM:
Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as…

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Oncology, Breast, Extracellular Matrix Research
3. Aug 2015

Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study

BACKGROUND:
During cancer the otherwise tightly controlled homeostasis of the extracellular matrix (ECM) is disturbed. The protein composition changes, the ECM stiffens and increased levels of proteases are secreted. The combination of these processes result in release of specific protein fragments…

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Respiratory System, Idiopathic Pulmonary Fibrosis
9. Jul 2015

Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders

OBJECTIVES:
Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the…

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Authors:

  • Kristensen JH,
  • Larsen L,
  • Dasgupta B,
  • Brodmerkel C,
  • Curran M,
  • Karsdal MA,
  • Sand JM,
  • Willumsen N,
  • Knox AJ,
  • Bolton CE,
  • Johnson SR,
  • Hägglund P,
  • Svensson B,
  • Leeming DJ,
Hepatic System, Non-Alcoholic Fatty Liver Disease
3. Jul 2015

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS

BACKGROUND AND AIMS:
Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human…

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Authors:

  • Nielsen MJ,
  • Lehmann J,
  • Leeming DJ,
  • Schierwagen R,
  • Klein S,
  • Jansen C,
  • Strassburg CP,
  • Bendtsen F,
  • Møller S,
  • Sauerbruch T,
  • Karsdal MA,
  • Krag A,
  • Trebicka J,
Respiratory System, Chronic Obstructive Pulmonary Disease
1. Jul 2015

Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD

Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development o…

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Chronic Obstructive Pulmonary Disease, Respiratory System
11. Jun 2015

Accelerated extracellular matrix turnover during exacerbations of COPD

BACKGROUND:
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progress…

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1. Jun 2015

Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study

BACKGROUND:
Idiopathic pulmonary fibrosis, a progressive and inevitably fatal disorder, has a highly variable clinical course. Biomarkers that reflect disease activity are urgently needed to inform patient management and for use as biomarkers of therapeutic response (theragnostic biomarkers) in cli…

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Authors:

  • Jenkins RG,
  • Simpson JK,
  • Saini G,
  • Bentley JH,
  • Russell AM,
  • Braybrooke R,
  • Molyneaux PL,
  • McKeever TM,
  • Wells AU,
  • Flynn A,
  • Hubbard RB,
  • Leeming DJ,
  • Marshall RP,
  • Karsdal MA,
  • Lukey PT,
  • Maher TM,
Hepatic System, Non-Alcoholic Fatty Liver Disease
15. May 2015

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential…

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Hepatic System, Alcoholic Liver Disease
1. May 2015

Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis

BACKGROUND AND AIMS:
The hepatic venous pressure gradient (HVPG) is an important but invasive diagnostic and prognostic marker in cirrhotic patients. The aim of the study was to evaluate a novel biochemical plasma marker of true type V collagen formation (Pro-C5) for describing HVPG.

METHODS:
N…

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Extracellular Matrix Research, Renal System, Chronic Renal Disease
26. Apr 2015

Turnover of type III collagen reflects disease severity and is associated with progression and microinflammation in patients with IgA nephropathy

BACKGROUND:
Renal fibrosis is the hallmark of progression to end-stage kidney disease. Non-invasive biomarkers of renal fibrosis could serve as specific end points in clinical trials and improve monitoring and stratification of patients with chronic kidney disease (CKD). To address this, we measure…

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Extracellular Matrix Research
1. Apr 2015

The importance of extracellular matrix for cell function and in vivo likeness

OBJECTIVE:
Fibrotic diseases may be described as a disease of the extracellular matrix, where the balance between matrix formation and degradation has been shifted leading to an accumulation of matrix. Currently a fit for purpose model and readily available approach are adapted when doing cell cult…

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Extracellular Matrix Research, Hepatitis B/C, Hepatic System
1. Feb 2015

Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C

BACKGROUND & AIMS:
Fibrogenesis results in release of certain extracellular matrix protein fragments into the circulation. We evaluated the diagnostic and prognostic performance of two novel serological markers, the precisely cleaved N-terminal propeptide of type III collagen (Pro-C3) and a peptide…

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Renal System, Extracellular Matrix Research
29. Oct 2014

Association of versican turnover with all-cause mortality in patients on haemodialysis

OBJECTIVE:
Cardiovascular diseases are among the most common causes of mortality in renal failure patients undergoing haemodialysis. A high turnover rate of the proteoglycan versican, represented by the increased presence of its fragmentation products in plasma, has previously been associated with …

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Respiratory System, Extracellular Matrix Research
29. Oct 2014

The role of extracellular matrix quality in pulmonary fibrosis

This review discusses the role of extracellular matrix (ECM) quality in the pathogenesis of pulmonary fibrosis (PF). In PF, the highly ordered structure of collagens and elastin within the ECM of the lung is severely disrupted and lacks its original tissue quality. Discussions about the ECM have foc…

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Oncology, Lung
3. Oct 2014

Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer

Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a…

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Hepatic System, Hepatitis B/C
29. Sep 2014

PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

BACKGROUND:
Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM)…

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Authors:

  • Jansen C,
  • Leeming DJ,
  • Mandorfer M,
  • Byrjalsen I,
  • Schierwagen R,
  • Schwabl P,
  • Karsdal MA,
  • Anadol E,
  • Strassburg CP,
  • Rockstroh J,
  • Peck-Radosavljevic M,
  • Møller S,
  • Bendtsen F,
  • Krag A,
  • Reiberger T,
  • Trebicka J,
Osteoarthritis
1. Sep 2014

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis

OBJECTIVE:
To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and loc…

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1. Sep 2014

Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers

OBJECTIVES:
Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade ex…

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Extracellular Matrix Research, Hepatic System
5. Aug 2014

Review article: the efficacy of biomarkers in chronic fibroproliferative diseases - early diagnosis and prognosis, with liver fibrosis as an exemplar

BACKGROUND:
Nearly 45% of all deaths are associated with chronic fibroproliferative diseases, of which the primary characteristic is altered remodelling of the extracellular matrix. A major difficulty in developing anti-fibrotic therapies is the lack of accurate and established techniques to estima…

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Bone, Rheumatology, Osteoarthritis
6. Jun 2014

ALPHA-CTX is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis

OBJECTIVE:
To evaluate joint tissue remodeling, with urinary collagen biomarkers, uALPHA CTX and uCTXII, and their association with osteoarthritis (OA) severity, progression, and localized knee bone turnover.

METHODS:
Participants (N=149) with symptomatic and radiographic knee OA underwent fixe…

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Renal System, Extracellular Matrix Research
28. Mar 2014

The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?

Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also…

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Respiratory System, Chronic Obstructive Pulmonary Disease
13. Dec 2013

MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis--validation of two novel biomarker assays

OBJECTIVES:
Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will re…

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Oncology, Pancreas
6. Nov 2013

Extracellular matrix specific protein fingerprints measured in serum can separate pancreatic cancer patients from healthy controls

BACKGROUND:
Pancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specifi…

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Renal System, Chronic Renal Disease
22. Aug 2013

Association of systemic collagen type IV formation with survival among patients undergoing hemodialysis

OBJECTIVE:
The 7S domain of collagen type IV (P4NP_7S) assessed in plasma represents systemic collagen type IV formation. The objective of the study was to investigate the association of systemic collagen type IV formation with survival among patients undergoing hemodialysis.

METHODS:
We perfor…

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Biomarker position
18. Aug 2013

Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways -- implications for modern clinical chemistry

The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…

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Rheumatology, Osteoarthritis
14. Aug 2013

Serological identification of fast progressors of structural damage with rheumatoid arthritis

INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…

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Rheumatology, Spondyloarthropathies
1. Aug 2013

Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis

Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural prote…

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Hepatic System, Alcoholic Liver Disease
30. Jul 2013

Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats

BACKGROUND:
Progression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM). Matrix-metalloproteinases (MMP) cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes). The levels of these neo-epitopes might refle…

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Cardiovascular System, Atherosclerosis
21. Jun 2013

Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

BACKGROUND:
Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated…

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Authors:

  • Skjøt-Arkil H,
  • Clausen RE,
  • Rasmussen LM,
  • Wang W,
  • Wang Y,
  • Zheng Q,
  • Mickley H,
  • Saaby L,
  • Diederichsen AC,
  • Lambrechtsen J,
  • Martinez FJ,
  • Hogaboam CM,
  • Han M,
  • Larsen MR,
  • Nawrocki A,
  • Vainer B,
  • Krustrup D,
  • Bjørling-Poulsen M,
  • Karsdal MA,
  • Leeming DJ,
Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …

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Rheumatology, Rheumatoid Arthritis
31. May 2013

Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways - implications for modern clinical chemistry

The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…

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Hepatic System
24. May 2013

Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model o2,454f liver fibrosis

Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis. Methods: Fibrogenesis was evaluated by quantitative histology and ci…

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Extracellular Matrix Research, Hepatic System
15. May 2013

Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases

BACKGROUND:
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and li…

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Hepatic System, Alcoholic Liver Disease
14. May 2013

Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model of liver fibrosis

Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis.

METHODS:
Fibrogenesis was evaluated by quantitative histology an…

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Authors:

  • Vassiliadis E,
  • Veidal SS,
  • Kristiansen MN,
  • Hansen C,
  • Jorgensen M,
  • Leeming DJ,
  • Karsdal M,
Hepatic System, Alcoholic Liver Disease
19. Apr 2013

The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters

AIM:
The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3).

METHODS:
The monoclonal antibody wa…

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Extracellular Matrix Research
11. Mar 2013

Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure

Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…

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Hepatic System, Alcoholic Liver Disease
3. Mar 2013

Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis--a serological evaluation

BACKGROUND/AIM:
We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis.

METHODS:
Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red stainin…

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Hepatic System, Alcoholic Liver Disease
13. Dec 2012

Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model

BACKGROUND:
Accumulation of extracellular matrix (ECM) and increased matrix metalloproteinase (MMP) activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl(4) treated animals with an ELISA de…

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Rheumatology, Spondyloarthropathies
17. Nov 2012

Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study

Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as bi…

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Respiratory System, Idiopathic Pulmonary Fibrosis, Chronic Obstructive Pulmonary Disease
20. Jul 2012

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

BACKGROUND:
Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in …

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Authors:

  • Skjøt-Arkil H,
  • Clausen RE,
  • Nguyen QH,
  • Wang Y,
  • Zheng Q,
  • Martinez FJ,
  • Hogaboam CM,
  • Han M,
  • Klickstein LB,
  • Larsen MR,
  • Nawrocki A,
  • Leeming DJ,
  • Karsdal MA,
Respiratory System, Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis
11. Jul 2012

Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis

In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin moti…

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Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012

Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker

BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…

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Hepatic System, Alcoholic Liver Disease
7. Jun 2012

Circulating levels of a collagen type v propeptide fragment in a carbon tetrachloride reversible model of liver fibrosis

AIM:
To measure levels of the collagen V formation marker CO5-1230 during liver fibrosis progression and regression.

METHODS:
Monoclonal antibodies were raised against the sequence TAALGDIMGH located at the start of the C-terminal propeptide between amino acid position 1230' and 1239' (CO5-1230…

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Rheumatology, Spondyloarthropathies
30. May 2012

Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis

OBJECTIVES:
Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a dia…

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Hepatic System, Alcoholic Liver Disease
16. May 2012

Enzyme-linked immunosorbent serum assay specific for the 7S domain of Collagen Type IV (P4NP 7S): A marker related to the extracellular matrix remodeling during liver fibrogenesis

AIM:
The present study describes the ability of a newly developed N-terminal pro-peptides of type IV collagen 7S domain (P4NP 7S) competitive enzyme-linked immunosorbent assay (ELISA) for describing liver fibrosis. The assay applies a monoclonal antibody specific for a PIVNP 7S epitope 100% homolog…

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Rheumatology, Spondyloarthropathies
7. May 2012

MMP mediated type V collagen degradation (C5M) is elevated in ankylosing spondylitis

OBJECTIVES:
Type V collagen has been demonstrated to control fibril formation. The aim of this study was to develop an ELISA capable of detecting a fragment of type V collagen generated by MMP-2/9 and to evaluate the assay as biomarker for ankylosing spondylitis (AS).

DESIGN AND METHODS:
A frag…

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Hepatic System, Alcoholic Liver Disease
5. Apr 2012

Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

AIM:
To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.

METHODS:
A monoclonal antibody against the sequence RLRSSVPGV-citrullin…

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Hepatic System, Extracellular Matrix Research
3. Jan 2012

Molecular serum markers of liver fibrosis

Fibrosis is a hallmark histologic event of chronic liver diseases and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patien…

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Bone
7. Nov 2011

Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options

Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the…

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Hematology
22. Oct 2011

Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

BACKGROUND:
Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of co…

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Journal:

Authors:

  • Veidal SS,
  • Karsdal MA,
  • Nawrocki A,
  • Larsen MR,
  • Dai Y,
  • Zheng Q,
  • Hägglund P,
  • Vainer B,
  • Skjøt-Arkil H,
  • Leeming DJ,
Hepatic System, Alcoholic Liver Disease
16. Oct 2011

A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)

A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and c…

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Journal:

Authors:

  • Leeming DJ,
  • He Y,
  • Veidal SS,
  • Nguyen Q,
  • Larsen D,
  • Koizumi M,
  • Segovia-Silvestre T,
  • Zhang C,
  • Zheng Q,
  • Sun S,
  • Cao Y,
  • Barkholt V,
  • Hägglund P,
  • Bay-Jensen A,
  • Qvist P,
  • Karsdal MA,
Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Aug 2011

Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis

AIM:
Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propeptide…

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Journal:

Authors:

  • Vassiliadis E,
  • Veidal SS,
  • Simonsen H,
  • Larsen DV,
  • Vainer B,
  • Chen X,
  • Zheng Q,
  • Karsdal MA,
  • Leeming DJ,
Hepatic System, Non-Alcoholic Fatty Liver Disease
9. Jun 2011

MMP mediated degradation of type VI collagen is highly associated with liver fibrosis--identification and validation of a novel biochemical marker assay

BACKGROUND AND AIMS:
During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragme…

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Extracellular Matrix Research
16. May 2011

Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and…

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Rheumatology, Osteoarthritis
13. Apr 2011

Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis

OBJECTIVES:
In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.

METHODS:
A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against…

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Rheumatology, Systemic Sclerosis
29. Mar 2011

Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis

BACKGROUND:
The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver…

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  • Vassiliadis E,
  • Veidal SS,
  • Barascuk N,
  • Mullick JB,
  • Clausen RE,
  • Larsen L,
  • Simonsen H,
  • Larsen DV,
  • bay,
  • Segovia-Silvestre T,
  • Leeming DJ,
  • Karsdal MA,
Hepatic System, Alcoholic Liver Disease
24. Mar 2011

Measurement of CO3-610, a potential liver biomarker derived from matrix metalloproteinase-9 degradation of collagen type III, in a rat model of reversible carbon-tetrachloride-induced fibrosis

BACKGROUND AND AIM:
The current study utilized a carbon tetrachloride (CCl(4))-induced liver fibrosis model to measure levels of the MMP9-mediated collagen type III degradation fragment CO3-610 (site of cleavage: KNGETGPQGP), during disease progression and regression, and to investigate a potential…

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Authors:

  • Vassiliadis E,
  • Larsen DV,
  • Clausen RE,
  • Veidal SS,
  • Barascuk N,
  • Larsen L,
  • Simonsen H,
  • Silvestre TS,
  • Hansen C,
  • Overgaard T,
  • Leeming DJ,
  • Karsdal MA,
Oncology, Bone
3. Mar 2011

Serum N-Terminal Propeptide of Collagen Type I is Associated with the Number of Bone Metastases in Breast and Prostate Cancer and Correlates to Other Bone Related Markers

BACKGROUND:
A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the …

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Bone, Osteoporosis
5. Oct 2010

Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)--assessment of corresponding epitopes

OBJECTIVES:
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP epitopes in the rat- and human species.

METHODS:
Monoclonal antibodies were raised again…

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Extracellular Matrix Research, Biomarker position
10. Jul 2010

Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers--are they the cause or the consequence of the disease?

The aim of this review is to discuss the potential usefulness of novel advances in the class of biochemical markers, neo-epitopes. Neo-epitopes are post-translational modifications (PTMs) of proteins formed by processes such as protease cleavage, citrullination, nitrosylation, glycosylation and isom…

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Bone, Osteoporosis
1. Jun 2010

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality

BACKGROUND:
Normal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly …

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Bone, Osteoporosis
20. Sep 2009

Is bone quality associated with collagen age?

The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not…

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Extracellular Matrix Research
14. May 2009

Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of prote…

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Bone, Osteoporosis
18. Nov 2008

Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation

BACKGROUND:
Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would h…

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Bone
19. Sep 2008

The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality

Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality.

INTRODUCTIO…

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Oncology, Bone
27. Jun 2008

Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

BACKGROUND:
Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in br…

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Rheumatology, Osteoarthritis
16. Jun 2008

Should subchondral bone turnover be targeted when treating osteoarthritis?

OBJECTIVE:
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This re…

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Bone, Osteoporosis
17. May 2008

Biochemical markers for monitoring response to therapy: evidence for higher bone specificity by a novel marker compared with routine markers

The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node …

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Bone, Osteoporosis
19. Mar 2008

Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies

Bone collagen maturation may be important for anti-fracture efficacy as the reduction in risk is only partly explained by a concomitant increase in BMD during anti-resorptive therapy. Different treatments caused diverse profiles in bone collagen degradation products, which may have implications for …

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Rheumatology, Osteoarthritis
13. Feb 2008

Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis

The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for prote…

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Bone
18. Jun 2007

Osteoclasts prefer aged bone

We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of age…

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Oncology, Bone
9. Dec 2006

Biochemical approach to the detection and monitoring of metastatic bone disease: What do we know and what questions need answers?

Metastatic spread to bones frequently occurs in several types of cancer diseases, in particular breast, prostate, and lung cancer. Infiltration of bone by tumour cells is a source of several complications including severe bone pain, spinal cord compression, hypercalcemia, pathologic fractures, all r…

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Bone, Osteoporosis
16. Aug 2006

An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice

BACKGROUND:
Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, …

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Oncology, Bone
15. Jul 2006

Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion

We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localiz…

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